Cross-sectional association study of hedonic hunger, self-control, cognitive distortion, and well-being with adiposity measures among a sample of urban Malaysian adults.

BACKGROUND: We assessed the association of hedonic hunger, self-control (impulsivity and restraint), cognitive distortion (CD), and well-being with adiposity measures such as waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body mass index (BMI), total body fat (TBF), subcutaneous fat (SF), visceral fat level (VFL), skeletal muscle percentage (SM), and resting metabolism (RM), among a sample of urban Malaysian adults at Sunway University and Sunway College, Selangor, Malaysia. METHODS: Among 186 participants (M/F = 51/135; aged 22.1 ± 5.0), psychometrics were assessed using Power of Food Scale (PFS), Brief Self-Control Scale, CD Questionnaire (CD-Quest), and WHO-5 Well-being Index. Blood pressures, anthropometrics and body compositions were also measured using standard methods and bioimpedance. RESULTS: Men had significantly higher well-being, but lower overall self-control, impulsivity and Food Available hedonic hunger. Those with moderate/severe CD had higher odds ratio (OR) of having high central adiposity, compared with those with absent/slight CD (OR: 2.52;95% CI: 1.14, 5.61; p = 0.023 for WC and OR: 2.50; 95% CI: 1.19, 5.23; p = 0.015 for WHR). Higher CD and PFS scores were strongly significantly correlated with higher systolic blood pressure (SBP), WC, WHR, WHtR, BMI, TBF, SF, VFL and RM. Lower self-control was weakly correlated with higher WC, while lower impulsivity and restraint were weakly correlated with higher VFL. Those who were overweight, obese, and in high TBF class had significantly higher PFS Aggregate Factor scores. Food Available and Food Present scores, but not Food Tasted, were also significantly higher among overweight participants. CONCLUSIONS: Higher hedonic hunger and CD were associated with higher SBP and all adiposity measures. Overweight participants had higher hedonic hunger in the context of ready availability and physical presence of highly palatable foods. Lower self-control was weakly correlated with higher central adiposity; lower impulsivity and restraint were weakly correlated with higher visceral adiposity. These findings have provided some insights into the cognitive factors underlying adiposity.

Atopic dermatitis-associated genetic variants regulate LOC100294145 expression implicating interleukin-27 production and type 1 interferon signaling.

Background: Atopic dermatitis (AD) is a complex inflammatory disease with a strong genetic component. A singular approach of genome wide association studies (GWAS) can identify AD-associated genetic variants, but is unable to explain their functional relevance in AD. This study aims to characterize AD-associated genetic variants and elucidate the mechanisms leading to AD through a multi-omics approach. Methods: GWAS identified an association between genetic variants at 6p21.32 locus and AD. Genotypes of 6p21.32 locus variants were evaluated against LOC100294145 expression in peripheral blood mononuclear cells (PBMCs). Their influence on LOC100294145 promoter activity was measured in vitro via a dual-luciferase assay. The function of LOC100294145 was then elucidated through a combination of co-expression analyses and gene enrichment with g:Profiler. Mendelian randomization was further used to assess the causal regulatory effect of LOC100294145 on its co-expressed genes. Results: Minor alleles of rs116160149 and rs115388857 at 6p21.32 locus were associated with increased AD risk (p = 2.175 × 10-8, OR = 1.552; p = 2.805 × 10-9, OR = 1.55) and higher LOC100294145 expression in PBMCs (adjusted p = 0.182; 8.267 × 10-12). LOC100294145 expression was also found to be increased in those with AD (adjusted p = 3.653 × 10-2). The genotype effect of 6p21.32 locus on LOC100294145 promoter activity was further validated in vitro. Co-expression analyses predicted LOC100294145 protein's involvement in interleukin-27 and type 1 interferon signaling, which was further substantiated through mendelian randomization. Conclusion: Genetic variants at 6p21.32 locus increase AD susceptibility through raising LOC100294145 expression. A multi-omics approach enabled the deduction of its pathogenesis model comprising dysregulation of hub genes involved in type 1 interferon and interleukin 27 signaling.

Sensitization to oil palm pollen associates with risks and severity of allergic diseases.

Background: Elaeis guineensis (Ela g, oil palm) pollen is one of the most predominant species of inhalant allergens in the tropical Southeast Asia region; however, its association with the manifestation of allergic diseases remains largely unexplored. This study aimed to determine the sensitization pattern of oil palm pollen and associate this with the risk and severity of allergic diseases. Methods: Participants were recruited as a part of the Singapore and Malaysia cross-sectional genetic and epidemiological study (SMCSGES). Two independent cohorts were recruited: n = 564 serum samples were collected and serological assessment was performed against a panel of 16 crude inhalant allergens including house dust mite, pet, insect, pollen, and fungal allergens; n = 13 652 Singapore/Malaysia Chinese young adults were recruited and skin prick test was used to assess oil palm sensitization, which was tested for its association with the risk and severity of asthma, allergic rhinitis (AR), and atopic dermatitis (AD). Results: The sensitization rate of oil palm pollen is 9.6% in the n = 564 Singapore/Malaysia cohort. In the n = 13 652 Singapore/Malaysia Chinese cohort, oil palm sensitization significantly associates with increased risks of asthma (p = 1.34x10-4), AR (p = 2.91x10-13), and AD (p = 6.95x10-7). Asthmatic patients with oil palm sensitization have increased risks of wheezing (p = 0.00995), nocturnal cough (p = 0.0122), and exacerbations (p = 0.00139) in the past 12 months. AR patients with oil palm sensitization also have an increased risk of developing moderate-to-severe symptoms (p = 0.00113). Conclusions: We have identified significant associations of oil palm sensitization with increased risks, exacerbations, and the severity of symptoms of allergic diseases in the tropical Southeast Asian region (Singapore/Malaysia).

Burgers, Fast Foods, and Increased Associated Risk for Atopic Dermatitis: A Cross-Sectional Study of Dietary Habits among Young Chinese Adults in Singapore/Malaysia.

BACKGROUND: We see increasing evidence that dietary and nutrients factors play a pivotal role in allergic diseases and recent global findings suggest that dietary habits influence the pathogenesis of atopic dermatitis (AD). Frequent consumption of fast food diets is associated with AD development. Despite the rising prevalence of AD in Asia, efforts in investigating the role of dietary habits and AD in adults are still lacking. METHODS: We evaluated the association between the dietary intake of 16 food types and AD manifestations using our Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES) population. Dietary habits profiles of 11,494 young Chinese adults (1,550 AD cases/2,978 non-atopic controls/6,386 atopic controls) were assessed by an investigator-administered questionnaire. AD cases were further evaluated for their chronicity (550 chronic) and severity (628 moderate-to-severe). Additionally, we derived a novel food index, Quality of Diet based on Glycaemic Index Score (QDGIS), to examine the association between dietary intake of glycaemic index (GI) and various AD phenotypes. RESULTS: The majority of AD subjects are distributed in the good (37.1%) and moderate (36.2%) QDGIS classes. From the multivariable analyses for age and gender, a moderate QDGIS class was significantly associated with a lower odds of AD (adjusted odds ratio (AOR): 0.844; 95% confidence interval (CI): 0.719-0.991; p < 0.05) and moderate-to-severe AD (AOR: 0.839; 95% CI: 0.714-0.985; p < 0.05). A good QDGIS class was only significantly associated with a lower odds of chronic AD (AOR: 0.769; 95% CI: 0.606-0.976; p < 0.05). Among high GI foods, frequent consumption of burgers/fast food was strongly associated with an increased risk of chronic and moderate-to-severe AD. Among low GI foods, increased intake frequencies of fruits, vegetables, and pulses decreased the odds of AD. Finally, we identified significant associations between frequent seafood, margarine, butter, and pasta consumption with an increased odds of AD despite them having little GI values. CONCLUSION: While genetic components are well-established in their risks associated with increased AD prevalence, there is still a lack of a focus epidemiology study associating dietary influence with AD. Based on the first allergic epidemiology study conducted here in Singapore and Malaysia, it laid the groundwork to guide potential dietary interventions from changing personal dietary habits.

The occurrence and probabilistic risk of exposure to parabens from bottled and hand-shaken teas in the general adult population of Taiwan.

Parabens (PBs) are esters of p-hydroxybenzoic acid, and there are growing concerns due to their potential to disrupt endocrine function and their wide use as preservatives in foodstuffs, including beverages. The consumption of bottled and hand-shaken teas is gradually replacing traditional tea consumption through brewing. However, no study has reported PB concentrations in different types of teas or packaging and their associated health risks. Our aim was to determine the concentration of PBs (methyl- (MetPB), ethyl- (EthPB), propyl- (PropPB), butyl-paraben (ButPB)) in green, black, and oolong teas in two varieties of products (bottled and hand-shaken teas), using UPLC-MS/MS. Additionally, we estimated the health risks associated with tea consumption in the general adult population of Taiwan. A Monte Carlo simulation was applied to estimate the distribution of daily PB intake through bottled (n = 79) and hand-shaken (n = 71) tea consumption. Our findings revealed geometric mean concentrations in bottled green/black/oolong teas were 714.1/631.2/532.1 ng/L for MetPB, 95.2/ 30.5/14.9 ng/L for EthPB, 77.9/28.3/non-detected (ND) ng/L for PropPB, and 69.3/26.6/ND ng/L for ButPB. Hand-shaken green/black/oolong teas exhibited concentrations of 867.5/2258/1307 ng/L for MetPB, 28.5/28.8/14.5 ng/L for EthPB, 25.4/18.3/17.8 ng/L for PropPB, and 30.3/18.0/15.5 ng/L for ButPB. The median MetPB concentrations in hand-shaken black (2333 ng/L) and oolong teas (1215 ng/L) were significantly higher than those in bottled black (595.4 ng/L) and oolong teas (489.3 ng/L). Conversely, median concentrations of EthPB, PropPB, and ButPB in bottled teas were significantly higher than those in hand-shaken teas. MetPB was the predominant PB, constituting 73.2-91.9% in bottled teas and 85-94% in hand-shaken teas. Our results showed no health risks associated with bottled or hand-shaken tea consumption based on reference doses. However, the study highlights the importance of continued vigilance given the potential chronic exposure to PBs from various sources, necessitating ongoing concern despite the absence of immediate risks from tea consumption.

A dietary pattern of frequent plant-based foods intake reduced the associated risks for atopic dermatitis exacerbation: Insights from the Singapore/Malaysia cross-sectional genetics epidemiology cohort.

BACKGROUND: The prevalence of atopic dermatitis (AD) has been increasing in recent years, especially in Asia. There is growing evidence to suggest the importance of dietary patterns in the development and management of AD. Here, we seek to understand how certain dietary patterns in a Singapore/Malaysia population are associated with various risks of AD development and exacerbation. METHODS: A standardized questionnaire following the International Study of Asthma and Allergies in Childhood (ISAAC) guidelines was investigator-administered to a clinically and epidemiology well-defined allergic cohort of 13,561 young Chinese adults aged 19-22. Information on their sociodemographic, lifestyle, dietary habits, and personal and family medical atopic histories were obtained. Allergic sensitization was assessed by a skin prick test to mite allergens. Spearman's rank-order correlation was used to assess the correlation between the intake frequencies of 16 food types. Dietary patterns were identified using principal component analysis. Four corresponding dietary scores were derived to examine the association of identified dietary patterns with allergic sensitization and AD exacerbations through a multivariable logistic regression that controlled for age, gender, parental eczema, BMI, and lifestyle factors. RESULTS: The correlation is the strongest between the intake of butter and margarine (R = 0.65). We identified four dietary patterns, "high-calorie foods", "plant-based foods", "meat and rice", and "probiotics, milk and eggs", and these accounted for 47.4% of the variance in the dietary habits among the subjects. Among these patterns, moderate-to-high intake of "plant-based foods" conferred a negative association for chronic (Adjusted odds ratio (AOR): 0.706; 95% confidence interval (CI): 0.589-0.847; p < 0.001) and moderate-to-severe AD (AOR: 0.756; 95% CI: 0.638-0.897; p < 0.01). "Meat and rice" and "probiotics, milk and eggs" were not significantly associated with AD exacerbation. While frequent adherence to "high-calorie foods" increased the associated risks for ever AD and moderate-to-severe AD, having a higher adherence to "plant-based foods" diminished the overall associated risks. CONCLUSIONS: Frequent adherence to "plant-based foods" was associated with reduced risks for AD exacerbation in young Chinese adults from Singapore/Malaysia. This provides the initial evidence to support the association between dietary factors and AD. Further research is needed to better understand the pathomechanisms underlying diet and AD exacerbations.

Dietary Protein Intake and Associated Risks for Atopic Dermatitis, Intrinsic Eczema, and Allergic Sensitization among Young Chinese Adults in Singapore/Malaysia: Key Findings from a Cross-sectional Study.

Through an investigator-administered questionnaire that follows the standard protocol of the International Study of Allergy and Asthma in Childhood, data on symptomatic histories of eczema and dietary habits were collected from 11,494 young Chinese adults in Singapore/Malaysia. Allergic sensitization status was assessed through a skin prick test reactivity to common house dust mites. Using three dietary indices (dietary protein score, animal protein score, and plant protein score), the associations between atopic dermatitis, intrinsic eczema, allergic sensitization, and intake of various proteins were estimated. On average, most subjects frequently eat meat, vegetables, and rice in their diets. Through a multivariable logistic regression adjusted for age, sex, body mass index, and parental eczema, subjects with high dietary protein score (adjusted OR = 1.397; 95% confidence interval = 1.133-1.724; P < 0.003) and high animal protein score (adjusted OR = 1.353; 95% confidence interval = 1.106-1.682; P < 0.003) were associated with increased risk of atopic dermatitis. Interestingly, synergy factor analysis revealed that a higher intake of plant proteins than animal proteins in diets significantly reduced overall associated risks of atopic dermatitis and allergic sensitization but not those of intrinsic eczema. Most importantly, these associations are independent of dietary fat intake. Taken together, frequent adherence to diets rich in plant proteins reduced associated risks of atopic dermatitis in Singapore/Malaysia Chinese adults.

A Dietary Pattern for High Estimated Total Fat Amount Is Associated with Enhanced Allergy Sensitization and Atopic Diseases among Singapore/Malaysia Young Chinese Adults.

INTRODUCTION: Frequent dietary patterns for fast food diets are suggested to be a risk factor for atopic disease development. Excessive dietary fats in fast foods are postulated to promote low-grade chronic inflammation. However, no studies in Asia have yet to characterize the dietary pattern for high-fat foods with atopic diseases. Thus, this study aims to assess the association between dietary fats with the prevalence of atopic diseases in an allergic cohort. METHODS: Through an investigator-administered questionnaire that follows the International Study of Asthma and Allergies in Childhood (ISAAC) protocol, we evaluated the eating habits, lifestyle behaviours, sociodemographics, and atopic symptoms, and history among 11,494 young Chinese adults in Singapore and Malaysia. A skin prick test (SPT) for common house dust mites was also conducted to determine the atopic (allergic) status. We identified 1,550 atopic dermatitis (AD), 1,301 allergic asthma (AS), and 3,757 allergic rhinitis (AR) atopic cases. We derived a novel dietary index, Diet Quality based on Total Fat Amount (DQTFA), to examine the association between eating patterns for estimated total fat amount with various atopic outcomes. RESULTS: There was a preponderance of subjects having positive SPT reaction (69.0%) with the prevalence of AR being the highest (32.7%), then AD (13.5%), and AS (11.3%). Additionally, there is a significantly higher proportion of subjects with an atopy background and atopic diseases consume diets with a high estimated mean fat amount. The adherence to a dietary pattern of the higher estimated total fat amount was shown to be strongly associated with all atopic diseases and exhibited dose-dependent responses in the univariate analysis. These associations remained significant even with the adjustments for age, gender, body mass index, use of alcohol, sedentary lifestyles, and physical activity. A dietary pattern for high-fat amount is more strongly associated with AS (adjusted odds ratio [AOR]: 1.524; 95% confidence interval [CI]: 1.216-1.725; p < 0.001) and AR (AOR: 1.294; 95% CI: 1.107-1.512; p < 0.001) compared to AD (AOR: 1.278; 95% CI: 1.049-1.559; p < 0.05). Finally, it was shown that having either one of the atopic comorbidities was strongly associated with a dietary pattern of high-fat amounts (AOR: 1.360; 95% CI: 1.161-1.594; p < 0.001). CONCLUSION: Our findings altogether provide initial evidence that the dietary pattern of a diet high in fat amount is associated with an increased risk of atopy and atopic diseases in young Chinese adults in Singapore and Malaysia. Balancing the consumption of dietary fats and changing personal dietary habits by choosing foods of the lower fat amount may reduce the associated odds of atopic diseases.

The ERBB2 Exonic Variant Pro1170Ala Modulates Mitogen-Activated Protein Kinase Signaling Cascades and Associates with Allergic Asthma.

INTRODUCTION: Previous studies have indicated the ERBB2 genetic variants in the 17q12 locus might be associated with asthma; however, the functional effects of these variants on asthma risk remain inconclusive. This study aimed to characterize the functional roles of asthma-associated ERBB2 single nucleotide polymorphisms (SNPs) in asthma pathogenesis by performing genetic association and functional analysis studies. METHODS: This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). Genotype-phenotype associations were assessed by performing a genotyping assay on n = 4,348 ethnic Chinese individuals from the SMCSGES cohort. The phosphorylation levels of receptors and signaling proteins in the MAPK signaling cascades, including ErbB2, EGFR, and ERK1/2, were compared across the genotypes of asthma-associated SNPs through in vitro and ex vivo approaches. RESULTS: The ERBB2 tag-SNP rs1058808 was significantly associated with allergic asthma, with the allele "G" identified as protective against the disease (adjusted logistic p = 6.56 × 10-9, OR = 0.625, 95% CI: 0.544-0.718). The allele "G" of rs1058808 resulted in a Pro1170Ala mutation that results in lower phosphorylation levels of ErbB2 in HaCat cells (p < 0.001), whereas the overall ERBB2 mRNA expression and the phosphorylation levels of EGFR remained unaffected. In the SMCSGES cohort, individuals carrying the genotype "GG" of rs1058808 had lower phosphorylated ERK1/2 proteins in the MAPK signaling cascade. A lower phosphorylation level of ERK1/2 was also associated with reduced asthma risk. CONCLUSIONS: The present findings highlighted the involvement of a functional exonic variant of ERBB2 in asthma development via modulating the MAPK signaling cascade.

Functional Polymorphisms of the Arachidonic Acid Pathway Associate with Risks and Clinical Outcomes of Allergic Diseases.

INTRODUCTION: The arachidonic acid (AA) pathway plays a crucial role in allergic inflammatory diseases; however, the functional roles of allergy-associated single nucleotide polymorphisms (SNPs) in this pathway remain incompletely illustrated. METHODS: This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). We performed population genotyping on n = 2,880 individuals from the SMCSGES cohort to assess the associations of SNPs in the AA pathway genes with asthma and allergic rhinitis (AR). Spirometry assessments were performed to identify associations between SNPs and lung function among n = 74 pediatric asthmatic patients from the same cohort. Allergy-associated SNPs were functionally characterized using in vitro promoter luciferase assay, along with DNA methylome and transcriptome data of n = 237 peripheral blood mononuclear cell (PBMC) samples collected from a subset of the SMCSGES cohort. RESULTS: Genetic association analysis showed 5 tag-SNPs from 4 AA pathway genes were significantly associated with asthma (rs689466 at COX2, rs35744894 at hematopoietic PGD2 synthase (HPGDS), rs11097414 at HPGDS, rs7167 at CRTH2, and rs5758 at TBXA2R, p < 0.05), whereas 3 tag-SNPs from HPGDS (rs35744894, rs11097414, and rs11097411) and 2 tag-SNPs from PTGDR (rs8019916 and rs41312470) were significantly associated with AR (p < 0.05). The asthma-associated rs689466 regulates COX2 promoter activity and associates with COX2 mRNA expression in PBMC. The allergy-associated rs1344612 was significantly associated with poorer lung function, increased risks of asthma and AR, and increased HPGDS promoter activity. The allergy-associated rs8019916 regulates PTGDR promoter activity and DNA methylation levels of cg23022053 and cg18369034 in PBMC. The asthma-associated rs7167 affects CRTH2 expression by regulating the methylation level of cg19192256 in PBMC. CONCLUSIONS: The present study identified multiple allergy-associated SNPs that modulate the transcript expressions of key genes in the AA pathway. The development of a "personalized medicine" approach with consideration of genetic influences on the AA pathway may hopefully result in efficacious strategies to manage and treat allergic diseases.

An update on the prevalence, chronicity, and severity of atopic dermatitis and the associated epidemiological risk factors in the Singapore/Malaysia Chinese young adult population: A detailed description of the Singapore/Malaysia Cross-Sectional Genetics Epidemiology Study (SMCGES) cohort.

Background: Atopic Dermatitis (AD) is a highly pruritic, chronic-recurrent inflammatory skin condition associated with erythematous lesions that affect a significant proportion of the population. Although AD is a non-communicable disease, it can cause pain, unbearable itchiness, sleep disturbance, loss of work productivity, and reduced quality of life. As a heterogeneous disease, AD is influenced by multiple genes and environmental triggers. As such, it is imperative to gain a deeper insight into the intricate gene-environment relationship that results in the manifestation of AD. Methods: There are 3 objectives in our study. We first aim to update the epidemiological status of AD amongst young adults in Singapore and Malaysia, in particular amongst the Chinese ethnic background. Next, we re-evaluated the possible associated risk factors, identified in our previous meta-analysis and review studies, on the current cohort. Finally, we described here a detailed disease presentation and symptoms profile of our Singapore and Malaysia Cross-Sectional Genetics Epidemiology Study (SMCGES) cohort, which forms the base population for the discovery of associated genetic factors in relation to asthma, allergic diseases and skin conditions. Based on a skin prick test (SPT) and investigator-administered medical history responses, we assessed the AD profiles of 11 494 participants and the significant modifiable and non-modifiable factors associated with disease presentation. Results: The prevalence of AD in the combined population was 13.5%. Chronic and moderate/severe AD were observed in 35.5% and 40.5% of the individuals with AD, respectively. Family history of atopic diseases, prior history of drug allergies, a history of acne, increased household family monthly income, higher number of individuals in the shared household, parental education, sedentary lifestyle, physical activities, alcoholic consumption, and even quality of diet was significantly associated with AD presentation, chronicity, and severity. Among all the factors evaluated, family and personal history of atopic diseases imposed the strongest associated risk. Conclusions: These findings supported our previous review studies and affirmed that familial history or genetic factors critically influence the development of AD in our population and environment. Environmental and other modifiable factors can also trigger AD throughout the lifetime of individuals who have especially inherited the atopic disease disposition. A better understanding of how these risk factors affect AD individuals in our population can facilitate disease surveillance, monitor disease control, and serve as a description for our future genetic epidemiology studies.

Allergic rhinitis in Chinese young adults from the Singapore/Malaysia cross-sectional genetics epidemiology study (SMCGES) cohort: Prevalence, patterns, and epidemiology of allergic rhinitis.

Background: Allergic rhinitis (AR) is characterized by the occurrence of at least 2 symptoms of nasal itching, nasal blockage, rhinorrhea, and sneezing, when not afflicted with a cold or flu, with defined atopic sensitization demonstrated by skin prick test or specific IgE responses. Besides the detriment to standard of living and economic burden of AR, both multicentre and single-cohort studies have observed an increase in AR prevalence in Asia over time. Methods: In total, 12 872 individuals, with mean age 22.1 years (SD = 4.8), were recruited from universities in Singapore and Malaysia. Each participant provided epidemiological data based on an investigator-administered questionnaire adapted from the validated International Study of Allergies and Asthma in Childhood (ISAAC) protocol, and atopy status was determined using a skin prick test (SPT) performed by qualified staff. AR was diagnosed according to Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines and a positive SPT result. Results: Sensitization (determined by SPT) to either Blomia tropicalis or Dermatophagoides pteronyssinus was prevalent in 66.5% of the cohort. Current rhinitis (manifesting ≥2 rhinitis symptoms, within the past 12 months) was observed in 48.9% of our population, while AR, which included atopy status, was estimated at 39.4%. Sneezing and rhinorrhea were the most common symptoms among AR cases. AR prevalence decreased with increasing age (OR: 0.979; 95% CI: 0.969-0.989), while male gender (OR: 2.053; 95% CI: 1.839-2.294), and a parental history of allergic diseases (OR: 2.750; 95% CI: 2.284-3.316) were significant risk factors for AR. Upon adjustment for age, gender, and parental history, housing type (OR: 0.632; 95% CI: 0.543-0.736) and income level (>$6000 vs <$2000; OR: 2.461; 95% CI: 2.058-2.947) remained as significant risk factors for AR, while ever having kept a pet (OR: 1.167; 95% CI: 1.025-1.328) emerged as a risk factor. Conflicting results were obtained for indicators of sedentary lifestyle: frequent physical activity (OR: 1.394; 95% CI: 1.150-1.694) and increased duration spent using the TV/computer (OR: 1.224; 95% CI: 1.006-1.489) both increased the risk of AR. Lastly, we used the Quality of Diet based on Glycaemic Index Score (QDGIS) to assess the Glycaemic Index (GI) level of overall diet. We identified lower GI level of overall diet as a protective factor against AR manifestation (OR: 0.682; 95% CI: 0.577-0.807). Conclusion: While the previously established non-modifiable risk factors for AR were present in our study population, the identification of modifiable risk factors, such as TV/computer usage, and dietary habits, opens a new area for research, both in the areas of gene-environment interaction, and management of AR.

Golgin A7 family member B (GOLGA7B) is a plausible novel gene associating high glycaemic index diet with acne vulgaris.

While the IGF1/FoxO1/mTORC1 signalling pathway is a well-established nutrigenomic link between high glycaemic index (GI)/glycaemic load (GL) diet and acne vulgaris, other signalling pathways remain elusive. Therefore, we aimed to investigate other genes that are involved in the high GI/GL diet-acne link, using our Singapore/Malaysia population epidemiological, genomics and transcriptomics data. High GI/GL dietary habit of 3207 acne cases (1869 and 1341 further classified into severity and scarring grades, respectively) and 2521 controls were evaluated based on Quality of Diet based on Glycaemic Index Score (QDGIS). Overlapping concordant differentially expressed genes (DEGs) between acne case-controls and QDGIS poor-moderate/good classes were identified from whole-transcriptome sequencing data of PBMC of a subset of participants. Finally, we assessed the expression quantitative trait loci (eQTL) association of single nucleotide polymorphisms (SNPs) of the concordant DEGs. Daily intake of fruits significantly reduced the risk of acne presentation, severity and scarring by up to 48.5%. Those with good QDGIS had significantly lower risk of mild and moderate/severe acne, and grade 1/2 acne scarring. Sequential filtering identified four overlapping concordant DEGs that were significantly associated with acne and QDGIS, namely GOLGA7B, SNCB, LOC102723849 and LOC283683. Combining transcriptome and genetic association data, we identified intronic SNP rs1953947 in GOLGA7B as an eQTL for acne. In conclusion, we identified GOLGA7B as a plausible novel gene that links high GI/GL with acne, and hence propose a model for the involvement of Golga7b in high GI/GL diet-acne pathogenesis, which includes palmitoyl acyltransferase zDHHC5, fatty acid translocase CD36 and palmitic acid.

Epidemiological Risk Factors Associated with Acne Vulgaris Presentation, Severity, and Scarring in a Singapore Chinese Population: A Cross-Sectional Study.

BACKGROUND: Acne vulgaris is classified based on the severity of skin lesions and post-healing scar types of these lesions. Numerous epidemiology studies have investigated the risk factors associated with acne presentation and severity, but studies for acne scarring are lacking. OBJECTIVE: To investigate the prevalence of acne, severity, and scarring grades and their associated risk factors among Singapore Chinese. METHODS: A total of 3,888 subjects (2,090 cases/1,798 controls; median age = 21 ± 4.589; range 17-71) completed an investigator-administered questionnaire as part of a cross-sectional study, which included sociodemographics, familial medical history, lifestyle factors, dietary habits, and acne history. Acne cases were further evaluated for their severity (n = 991) and scarring (n = 988) grades by a trained personnel. RESULTS: The majority of the acne cases had mild acne/grade 1 scarring, while less than 1% had severe acne/grade 4 scarring. Parental acne was significantly associated with acne presentation and moderate/severe acne, while sibling acne was significantly associated with grade 3/4 scarring. Gender and age affected acne severity and scarring but not acne presentation, while tertiary maternal education level and the possession of ≥3 siblings were particularly associated with acne scarring. Underweight BMI was protective against acne presentation, while atopic diseases (asthma, allergic rhinitis, eczema) were its predisposing factors. Of the evaluated lifestyle factors, computer/TV usage had significant association with acne presentation, while alcohol consumption was significantly associated with acne severity. Frequent milk consumption was associated with a protective effect for moderate-severe acne, while frequent butter consumption had a detrimental effect on acne scarring extent. CONCLUSION: Positive familial history is a strong predisposing factor in determining acne presentation, severity, and scarring. Demographic factors (gender, age) and sedentary lifestyle (increased computer/TV usage) influence acne presentation, while dietary habits (milk and butter consumption) influence acne severity and scarring. The predisposing factors revealed in this study could help us to gain insights into acne pathophysiology and hence develop interventions especially targeting modifiable risk factors.

Functional variants in the chromosome 4q21 locus contribute to allergic rhinitis risk by modulating the expression of N-acylethanolamine acid amidase.

BACKGROUND: Previous haplotype-based association studies identified chromosome 4q21 as an allergic rhinitis (AR) susceptibility locus; however, the functional role of 4q21 single nucleotide polymorphisms (SNPs) on AR risk remains unclear. OBJECTIVE: To investigate the functional effect of 4q21 SNPs on AR risk by conducting cohort-based functional genomics and genetic association analyses. METHODS: The associations between 4q21 SNPs and mRNA expression levels of three 4q21-associated genes (SDAD1, NAAA and CXCL9) in peripheral blood mononuclear cells (PBMCs) were assessed in a Singapore/Malaysia Chinese cohort (n = 291). Exon expression levels of these genes in PBMCs were tested against the tag-SNP genotypes in a Singapore Chinese cohort (n = 30). Serum protein levels of these genes were assessed with tag-SNP genotypes in a Singapore Chinese cohort (n = 193). SNP functions were characterized through luciferase assay. In a Singapore Chinese cohort (n = 1794), we confirmed the associations between functional SNPs and AR. RESULTS: Forty SNPs in 4q21 showed significant associations with NAAA (but not SDAD1 or CXCL9) mRNA expression in PBMCs, of which were tagged by two tag-SNPs, rs17001237 and rs2242470. Both tag-SNPs rs2242470 and rs12648687 (a proxy for rs17001237) were also significantly associated with the expression level of NAAA exon 1. Tag-SNP rs12648687 was correlated with serum NAAA level. A four promoter SNPs-haplotype tagged by rs17001237 influenced the NAAA promoter activity in HEK293T cells. Lastly, individuals carrying the risk allele A of rs12648687 exhibited significantly higher AR risk in the Singapore Chinese population. CONCLUSIONS & CLINICAL RELEVANCE: The rs17001237 linkage set SNPs in the 4q21 locus are associated with NAAA expression at both gene and protein levels ex vivo, have functional consequences in vitro and contribute to AR susceptibility in our study population. Our findings provided a better understanding of the genetic mechanism that contributes to AR pathogenesis.

Sensitization to Airborne Fungal Allergens Associates with Asthma and Allergic Rhinitis Presentation and Severity in the Singaporean/Malaysian Population.

Fungal spores and conidia are the major components of total airspora in the tropical Asia environment, and their sensitization patterns are often associated with allergic diseases such as asthma, allergic rhinitis (AR), and atopic dermatitis. Hence, we recruited a cross-sectional cohort of 9223 Singapore/Malaysia Chinese adults and assessed their sensitization against Curvularia lunata allergen using the skin prick test approach. A subset of this cohort (n = 254) was also screened for specific Immunoglobulin E (sIgE) titers against a panel of 11 fungal allergens. We found significant association of Curvularia lunata sensitization with the risk of asthma (OR = 1.66, 95% CI: 1.17-2.33; p = 0.00391) and AR (OR = 1.69, 95% CI: 1.18-2.41; p = 0.00396). Among asthmatic patients (n = 1680), Curvularia lunata sensitization also increased frequencies of wheezing symptoms (OR = 1.81, 95% CI: 1.05-2.96; p = 0.0239), general practitioner/specialist visits (OR = 2.37, 95% CI: 1.13-4.61; p = 0.0157), and other asthma-related exacerbation events (OR = 2.14, 95% CI: 1.04-4.10; p = 0.0289). In our serum cohort, sensitization to Aspergillus spp. was the most common fungal sensitization, with 23.6% (n = 60) had a class 3 and above sensitization (positive sensitization; sIgE titers of > 3.5 kU/L) against this allergen. Increasing sIgE titer against Aspergillus spp. was also correlated with increased AR risk and AR-related symptoms. In conclusion, our findings emphasize an important role of fungal sensitization in the manifestations of asthma and AR in the Southeast Asian Chinese population.

Gene variants associated with acne vulgaris presentation and severity: a systematic review and meta-analysis.

BACKGROUND: Multiple factors have been attributed to acne vulgaris predisposition and individual variations in the severity of skin symptoms, and genetics stood out as one of the major factors. METHODS: We performed a systematic review on the genes and their variants that have been investigated for association with acne presentation and severity. A random-effect meta-analysis using the allele model (minor allele vs. major allele) was also conducted to provide an overall estimation of risk effects of frequently reported gene variants. This included a subset data of 982 acne cases and 846 controls extracted from our existing GWAS database on various allergic and skin diseases among Singapore Chinese. RESULTS: Systematic review of 51 articles covering Asians and Caucasians found 60 genes/loci and their 100 variants implicated in acne; majority of them were in the intron, coding region/missense, and promoter regions. The commonly studied candidate genes/gene families include tumor necrosis factor (TNF), and the interleukin (IL) and cytochrome P450 (CYP) gene families. Our meta-analysis showed that most of the analyzed gene variants exhibited insignificant pooled odds ratio (pOR) and significant heterogeneity between studies. Nevertheless, we found that TNF rs1800629 A allele carriers and CYP17A1 rs743572 T allele carriers had significantly reduced mild acne risk [pOR: 0.60; 95% Confidence Interval (CI): 0.33-0.86] and severe acne risk (pOR: 0.59; 95% CI: 0.40-0.79), respectively, across populations. Overall, FST (follistatin) rs629725 A allele poses a significantly modest increased risk for acne presentation (pOR: 1.19, 95% CI: 1.14, 1.23), but neither TIMP2 (TIMP metallopeptidase inhibitor 2) rs8179090 nor CYP1A1 rs4646903 (pOR: 0.96, 95% CI: 0.80-1.12; pOR: 0.95, 95% CI: 0.83, 1.08), respectively. We discovered 15 novel SNPs in the 3' UTR region of the Toll-like Receptor 4 gene (TLR4) associated with acne presentation. CONCLUSIONS: This systematic review and meta-analysis suggest that genes influencing inflammatory responses, specifically TNF, and genes influencing the function and activity of sebaceous glands, specifically CYP17A1 and FST, have potential risk variants for acne presentation and severity across populations. Understanding the genetic susceptibility factors and biological pathways involved in the pathogenesis of acne will help us to gain insights into developing effective acne treatments.

Modifiable and non-modifiable epidemiological risk factors for acne, acne severity and acne scarring among Malaysian Chinese: a cross-sectional study.

BACKGROUND: Acne vulgaris, a highly prevalent multifactorial inflammatory skin disease, can be categorised into different severity and scarring grades based on the type, number, and severity of lesions. While many epidemiology studies have investigated the risk factors for acne presentation, fewer studies have specifically studied the risk factors for acne severity and scarring. Therefore, this study investigated the prevalence of acne, acne severity and scarring grades, and their associated non-modifiable and modifiable epidemiological risk factors among Malaysian Chinese. METHODS: A total of 1840 subjects (1117 cases/723 controls) completed an investigator-administered questionnaire as part of a cross-sectional study, which include socio-demographics, familial history, lifestyle factors, dietary habits, and acne history. Acne cases were further evaluated for their severity (n = 1051) and scarring (n = 1052) grades by a trained personnel. RESULTS: Majority of the acne cases (up to 69%) had mild acne or Grade 1/2 scarring, while 21.6% had moderate/severe acne and 5.5% had Grade 3/4 scarring. Males had significantly higher risk of presenting with higher grades of acne scarring. Those who had acne, regardless of severity and scarring grades, had strong positive familial history (either in parents and/or sibling). Frequent consumption (most or all days) of foods that are commonly consumed during breakfast (butter, probiotic drinks, cereals and milk) decreased the risk for acne presentation and higher acne scarring, while periodic consumption (once/twice per week) of nuts and burgers/fast food decreased the risk for higher acne severity. Alcohol drinking was significantly associated with increased risk for acne presentation, while paternal, parental and household smoking were associated with reduced risk of more severe acne. CONCLUSIONS: In conclusion, positive familial history is a strong predisposing factor in influencing acne presentation, severity and scarring. Frequent consumption of foods that are commonly consumed during breakfast is protective against acne presentation.

IgE-binding residues analysis of the house dust mite allergen Der p 23.

House dust mites (HDMs) are one of the major causes of allergies in the world. The group 23 allergen, Der p 23, from Dermatophagoides pteronyssinus, is a major allergen amongst HDM-sensitized individuals. This study aims to determine the specific immunoglobulin E (sIgE) binding frequency and IgE-binding residues of recombinant Der p 23 (rDer p 23) allergen amongst a cohort of consecutive atopic individuals in a tropical region. We performed site-directed mutagenesis and carried out immuno-dot blot assays using 65 atopic sera. The immuno-dot blot assays results indicated that the two residues K44 and E46 which are located at the N-terminal region are the major IgE-binding residues. The rDerp-23 sIgE titers are strongly correlated to the number of IgE-binding residues for rDer p 23 (P < 0.001). Atopic individuals who were only sensitized to HDM have a significantly higher number of IgE-binding residues than the individuals who were polysensitized to HDM and other crude allergens (P < 0.05). Individuals with allergic multimorbidity and moderate-to-severe allergic rhinitis also have a higher number of IgE-binding residues compared to those with single allergic disease and mild allergic rhinitis. The results prompt us to hypothesize that the individuals who have a higher number of IgE-binding residues may face a bigger challenge to be treated through immunotherapy due to the complexity in designing an effective hypoallergen with a high number of IgE-binding residues. We propose that the development of a refined molecular diagnostic assay, which includes alanine substitution of surface-exposed residues could be a more precise diagnostic strategy to identify all the IgE-binding residues of a major allergen for an atopic individual and the development could be another new dimension in allergy diagnosis and allergen immunotherapy treatment.

Crystal structure and epitope analysis of house dust mite allergen Der f 21.

Group 21 and 5 allergens are homologous house dust mite proteins known as mid-tier allergens. To reveal the biological function of group 21 allergens and to understand better the allergenicity of the rDer f 21 allergen, we determined the 1.5 Å crystal structure of rDer f 21 allergen from Dermatophagoides farinae. The rDer f 21 protein consists of a three helical bundle, similar to available structures of group 21 and homologous group 5 allergens. The rDer f 21 dimer forms a hydrophobic binding pocket similar to the one in the Der p 5 allergen, which indicates that both of the homologous groups could share a similar function. By performing structure-guided mutagenesis, we mutated all 38 surface-exposed polar residues of the rDer f 21 allergen and carried out immuno-dot blot assays using 24 atopic sera. Six residues, K10, K26, K42, E43, K46, and K48, which are located in the region between the N-terminus and the loop 1 of rDer f 21 were identified as the major IgE epitopes of rDer f 21. Epitope mapping of all potential IgE epitopes on the surface of the rDer f 21 crystal structure revealed heterogeneity in the sIgE recognition of the allergen epitopes in atopic individuals. The higher the allergen-sIgE level of an individual, the higher the number of epitope residues that are found in the allergen. The results illustrate the clear correlation between the number of specific major epitope residues in an allergen and the sIgE level of the atopic population.