The association between iron and vitamin D status in Arab adolescents.

OBJECTIVE: Both vitamin D and Fe micronutrient deficiencies are common in Saudi Arabia but the association between them is unclear. The present study aimed to determine whether Fe indices are associated with vitamin D status and other metabolic markers in Arab adolescents. DESIGN: Single-centre, cross-sectional study gathering anthropometrics, glucose and lipid profile. Serum 25-hydroxyvitamin D (25(OH)D), Fe, total iron-binding capacity (TIBC), transferrin saturation (%) and other parameters were measured. SETTING: Vitamin D School Project Database, King Saud University (2014-2016). PARTICIPANTS: Arab adolescents aged 10-17 years randomly selected from the Vitamin D School Project Database (170 Saudi students; 100 girls, seventy boys). RESULTS: Among Fe indices, only TIBC was found to be significantly and inversely associated with 25(OH)D (r = -0·20; P < 0·01) and only in girls (r = -0·20; P < 0·05). Among cardiometabolic parameters, serum Fe was associated with TAG in boys (r = 0·36; P < 0·01) and inversely associated with HDL-cholesterol in girls (r = -0·29; P < 0·05). Age was the most significant predictor of serum Fe for all participants, accounting for 5 % (R2 = 0·05; P = 0·004) of variance perceived. Serum 25(OH)D and age, on the other hand, were the most significant predictors for TIBC, accounting for 10·1 % (R2 = 0·10; P < 0·001) of variance perceived. CONCLUSIONS: Among healthy Arab adolescents, the association between vitamin D and Fe indices, particularly TIBC, is modest, inverse and sex-dependent. Larger studies with inclusion of markers such as hepcidin and ferritin, vitamin D metabolites and endogenous sex hormones may provide a clearer view of this complex association.

Strong parent-child correlation in circulating vitamin B12 levels and its association with inflammatory markers in Saudi families.

Vitamin B12 deficiency leads to adverse effects on human health, but limited information is available as to whether abnormal vitamin B12 levels are associated between parents and offspring. The present study aimed to assess the association between circulating levels of vitamin B12 in Saudi parents and their children as well as its association with pro-inflammatory markers. A total of 104 Saudi families: 49 fathers, 63 mothers, 94 sons and 79 daughters were selected for the study. Fasting blood samples and anthropometrics were collected. Biochemical parameters, various pro-inflammatory markers and vitamin B12 were measured. Results showed a significant positive correlation between B12 levels in most parent-offspring pairs: mother-daughter (N = 46 pairs, r = 0.72, p < 0.0001); father-daughter (N = 39, r = 0.62, p < 0.0001) and mother-son (N = 51, r = 0.42, p < 0.01). This association was absent in father-son pairs (N = 48, r = 0.26, p = 0.09). Also, B12 was inversely associated with tumor necrosis factor-α and plasminogen activator inhibitor-1 in parents (r = -0.32; p < 0.01 and r = -0.31; p < 0.01 respectively) and children (r = -0.14; p < 0.01 and r = -0.19; p < 0.01 respectively). A significant inverse correlation was found between vitamin B12 and leptin in mothers (r = -0.31, p < 0.05). Our study suggests a strong familial component between B12 levels indicating a possible genetic influence on individual B12 status. Our study also suggests an inverse correlation between circulating levels of vitamin B12 and pro-inflammatory markers. The present study highlights the importance of extending screening in families of patients with abnormal B12 levels and expanding treatment, if necessary, to maximize clinical benefits.

Susceptibility to type 2 diabetes may be modulated by haplotypes in G6PC2, a target of positive selection.

BACKGROUND: The endoplasmic reticulum enzyme glucose-6-phosphatase catalyzes the common terminal reaction in the gluconeogenic/glycogenolytic pathways and plays a central role in glucose homeostasis. In most mammals, different G6PC subunits are encoded by three paralogous genes (G6PC, G6PC2, and G6PC3). Mutations in G6PC and G6PC3 are responsible for human mendelian diseases, whereas variants in G6PC2 are associated with fasting glucose (FG) levels. RESULTS: We analyzed the evolutionary history of G6Pase genes. Results indicated that the three paralogs originated during early vertebrate evolution and that negative selection was the major force shaping diversity at these genes in mammals. Nonetheless, site-wise estimation of evolutionary rates at corresponding sites revealed weak correlations, suggesting that mammalian G6Pases have evolved different structural features over time. We also detected pervasive positive selection at mammalian G6PC2. Most selected residues localize in the C-terminal protein region, where several human variants associated with FG levels also map. This region was re-sequenced in ~560 subjects from Saudi Arabia, 185 of whom suffering from type 2 diabetes (T2D). The frequency of rare missense and nonsense variants was not significantly different in T2D and controls. Association analysis with two common missense variants (V219L and S342C) revealed a weak but significant association for both SNPs when analyses were conditioned on rs560887, previously identified in a GWAS for FG. Two haplotypes were significantly associated with T2D with an opposite effect direction. CONCLUSIONS: We detected pervasive positive selection at mammalian G6PC2 genes and we suggest that distinct haplotypes at the G6PC2 locus modulate susceptibility to T2D.

Sex-specific vitamin D effects on blood coagulation among overweight adults.

BACKGROUND: Overweight adults are at increased risk for cardiovascular disease and vitamin D deficiency, whereas an important feature to vitamin D physiology is its sex dependence. The aim of this study was to examine whether vitamin D status improvement exerts a sexually dimorphic effect on serum proteins associated with cardiovascular risk among overweight adults. MATERIALS AND METHODS: Unprocessed serum from age- and BMI-matched men (n = 26) and premenopausal women (n = 24) with vitamin D deficiency and after they achieved sufficiency through a 12-month nutritional intervention was analysed using our previously published depletion-free quantitative proteomics method. Key findings were verified with ELISA. Differentially expressed proteins were subjected to in silico bioinformatics assessment using principal component analysis, hierarchical clustering and Metacore™ pathway analysis. All mass spectrometry proteomic data are available via ProteomeXchange (identifier: PXD003663). RESULTS: A total of 282 proteins were differentially expressed after the intervention between men and women (P-value ≤ 0·05), in which the blood coagulation pathway was significantly enriched. In agreement with the proteomics findings, ELISA measurements showed vitamin K-dependent protein C, von Willebrand factor, fibrinogen gamma chain and multimerin-1 proteins, of relevance to blood coagulation, to be differentially affected (P-value ≤ 0·05) between sexes after vitamin D status correction. CONCLUSIONS: This study identified novel protein-level molecular indicators on the sexually dimorphic effect of vitamin D status correction associated with blood coagulation among overweight adults. These sex-mediated vitamin D effects should be factored in the design and interpretation of vitamin D observational and interventional studies testing cardiometabolic outcomes.

SNPs in FNDC5 (irisin) are associated with obesity and modulation of glucose and lipid metabolism in Saudi subjects.

BACKGROUND: Irisin is a recently identified myokine that plays an important role in preventing obesity and insulin resistance. We investigated whether the common FNDC5 (irisin precursor) gene variants influence susceptibility to obesity and type 2 diabetes (T2D) and verified the impact of FNDC5 gene variants on serum irisin levels, glucose and lipid metabolism in a Saudi population. METHODS: Genomic DNA from 814 (394 T2DM and 414 controls) subjects were genotyped for the five common SNPs (rs3480A/G, rs1746661G/T, rs1298190A/G, rs726344A/G and rs1570569G/T) of the FNDC5 gene using the TaqMan genotyping assay. Biochemical parameters and hematic concentrations of irisin and insulin as well as anthropometric indices were collected. RESULTS: Serum irisin levels were higher in T2DM patients compared to controls (p < 0.0001). Analyses of FNDC5 SNPs showed that: 1) The rs3480 GG associates with decreased risk of obesity (p = 0.005; odds ratio: 0.48) and lower body mass index (BMI) values (p = 0.03). In addition, GGAAG was identified as the protective haplotype against risk of obesity (p = 0.001; odds ratio: 0.23). 2) The rs1746661 G allele associates with higher triglyceride (TG) levels (p = 0.019). 3) The rs157069 TT genotype associates with higher fasting insulin (p = 0.029) and HOMA-IR (p = 0.002) as well as with lower circulating irisin levels (p = 0.016). CONCLUSIONS: SNPs in FNDC5 gene correlates with obesity and glucose-lipid metabolism possibly because they modulate the serum levels of irisin.

Deleterious effects of incense smoke exposure on kidney function and architecture in male albino rats.

CONTEXT: Previous studies, including ours, have shown adverse effects of incense smoke on human health. However, the effect of incense smoke on kidney function and structure remains unknown. OBJECTIVE: To evaluate possible adverse effects of incense smoke on kidney function and architecture in albino rats after chronic exposure to Arabian incense. MATERIALS AND METHODS: Emission characteristics including particle size distribution, volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) were determined by gravimetric and GCMS analyses. Kidney functional markers, oxidative stress and inflammatory markers were measured by standard or ELISA based procedures. Ultrastructural changes in kidney were examined by transmission electron microscope (TEM) and the gene expression of xenobiotic metabolizing enzymes including cytochrome P-450-1A1 (CYP1A1) and CYP1A2 were studied by real time PCR. RESULTS: Rats exposed to incense smoke demonstrated a significant increase in serum creatinine, uric acid, blood urea nitrogen (BUN), tissue malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-4 (IL-4) levels and a significant decline in tissue reduced glutathione (GSH) and catalase activity. Incense smoke exposed rats also displayed marked ultrastructural changes in kidney tissue. Further, a significant increase in tissue gene expression of both CYP1A1 and CYP1A2 was noted in exposed rats. DISCUSSION: Changes to kidney functional markers and architecture appear to be mediated through augmented oxidative stress and inflammation. CONCLUSION: Long-term exposure to incense smoke may have deleterious effects on kidney function and architecture. Though, inhalation is the rout of exposure, findings of this study underscore that incense smoke may also have an effect on non-pulmonary tissues.

Sensitivity of various adiposity indices in identifying cardiometabolic diseases in Arab adults.

BACKGROUND: Obesity is a recognized risk factor for various cardiometabolic diseases and several indices are used clinically to assess overall cardiometabolic risk. This study aims to determine the sensitivity of six anthropometric indices [Body mass index (BMI), waist, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body adiposity index (BAI) and visceral adiposity index (VAI)] in determining diabetes mellitus type 2, coronary heart disease, dyslipidemia, hypertension and metabolic syndrome (MetS) in Saudi adults recruited from two independent cohorts (2008-2009 and 2013-2014). METHODS: A total of 6,821 Saudi adults [2008-2009, N = 3,971 (1,698 males and 2,273 females); 2013-2014, N = 2,850 (926 males and 1,924 females)] aged 18-70 years old were included in this descriptive, cross-sectional study. Anthropometrics were obtained and fasting blood samples analyzed for glucose and lipids. BMI, WHR, WHtR, BAI and VAI were computed mathematically. RESULTS: VAI was the most sensitive index in determining DMT2 (AUC 0.72; p < 0.001) in the 2008-2009 cohort and MetS (AUC = 0.84; p < 0.001) in the 2013-2014 cohort. WHR was most discriminating for CHD in both cohorts (AUC 0.70 and 0.84 for 2008-2009 and 2013-2014, p values <0.001, respectively). WHtR was most sensitive but rather modest in determining hypertension (AUC 0.66; p < 0.001), while waist circumference was most sensitive for dyslipidemia (AUC 0.72; p < 0.001) in the 2008-2009 cohort and MetS (AUC 0.85; p < 0.001) in the 2013-2014 cohort. BAI was the least sensitive adiposity index. CONCLUSION: Sensitivity of adiposity indices regarding cardiometabolic diseases highlight the importance of body fat distribution in determining overall cardiometabolic risk, with indices involving abdominal obesity being more clinically significant than BMI and BAI. The sensitivity of these adiposity indices should be noted in assessing a particular cardiometabolic disease.

Habitual physical activity is associated with circulating irisin in healthy controls but not in subjects with diabetes mellitus type 2.

BACKGROUND: Irisin, a novel myokine, has been shown to increase following vigorous exercise, with studies suggesting that it mediates some of the beneficial effects of exercise. Irisin might play a role in 'browning' of white adipocytes, thus increasing energy expenditure. The role of irisin in exercise and energy expenditure in subjects with diabetes mellitus type 2 (DMT2) remains largely unknown. We aimed to investigate the association between circulating irisin and habitual physical activity in subjects with and without DMT2. MATERIAL AND METHODS: In this cross-sectional study, 164 Saudi adults: 81 non-DMT2 controls [age: (mean ± SD) 51.6 ± 10.9; BMI: 29.6 ± 4.3 kg/m(2) ] and 83 DMT2 subjects [age: 54.3 ± 10.3 year; BMI: 29.4 ± 4.7 kg/m(2) ] were studied. Anthropometric and fasting serum biochemical data were collected. Circulating irisin was measured using an enzyme-linked immunosorbent assay (ELISA). Frequency intensity time (FIT) index was used to assess the level of habitual physical activity. RESULTS: We observed significantly higher levels of irisin in DMT2 subjects than in controls (P < 0.001). FIT index was positively associated (r = 0.20, P = 0.03) with circulating irisin in controls only. Additionally, irisin levels were significantly higher in tertile 3 (0.75 ± 0.07 µg/mL) than tertile 1 (0.49 ± 0.06 µg/mL) of the FIT index in healthy controls, whilst no such relation with physical activity was observed in DMT2 subjects. CONCLUSION: This cross-sectional study has shown a weak association of irisin with physical activity levels in healthy controls but not in DMT2 subjects, suggesting the possibility of discordant regulation in the condition of DMT2.

A nonsense polymorphism (R392X) in TLR5 protects from obesity but predisposes to diabetes.

The TLR5 gene encodes an innate immunity receptor. Mice lacking Tlr5 (T5KO) develop insulin resistance and increased adiposity. Owing to the segregation of a dominant nonsense polymorphism (R392X, rs5744168), a portion of humans lack TLR5 function. We investigated whether the nonsense polymorphism influences obesity and susceptibility to type 2 diabetes (T2D). R392X was genotyped in two cohorts from Saudi Arabia, a region where obesity and type 2 diabetes (T2D) are highly prevalent. The nonsense allele was found to protect from obesity (p(combined) = 0.0062; odds ratio, 0.51) and to associate with lower body mass index (BMI) (p(combined) = 0.0061); this allele also correlated with a reduced production of proinflammatory cytokines. A significant interaction was noted between rs5744168 and sex in affecting BMI (p(interaction) = 0.006), and stratification by gender revealed that the association is driven by females (p(combined) = 0.0016 and 0.0006 for obesity and BMI, respectively). The nonsense polymorphism also associated with BMI in nonobese women. After correction for BMI, the 392X allele was found to represent a risk factor for T2D with a sex-specific effect (p(interaction) = 0.023) mediated by females (p = 0.021; odds ratio, 2.60). Fasting plasma glucose levels in nondiabetic individuals were also higher in women carrying the nonsense allele (p = 0.012). Thus, in contrast to T5KO mice, loss of human TLR5 function protects from weight gain, but in analogy to the animal model, the nonsense allele predisposes to T2D. These effects are apparently sex-specific. Data in this study reinforce the hypothesis that metabolic diseases, including T2D, are associated with immune dysregulation.

Whole serum 3D LC-nESI-FTMS quantitative proteomics reveals sexual dimorphism in the milieu intérieur of overweight and obese adults.

Linking gender-specific differences to the molecular etiology of obesity has been largely based on genomic and transcriptomic evidence lacking endophenotypic insight and is not applicable to the extracellular fluid compartments, or the milieu intérieur, of the human body. To address this need, this study profiled the whole serum proteomes of age-matched nondiabetic overweight and obese females (n = 28) and males (n = 31) using a multiplex design with pooled biological and technical replicates. To bypass basic limitations of immunodepletion-based strategies, subproteome enrichment by size-exclusion chromatography (SuPrE-SEC) followed by iTRAQ 2D-LC-nESI-FTMS analysis was used. The study resulted in the reproducible analysis of 2472 proteins (peptide FDR < 5%, q < 0.05). A total of 248 proteins exhibited significant modulation between men and women (p < 0.05) that mapped to pathways associated with ß-estradiol, lipid and prostanoid metabolism, vitamin D function, immunity/inflammation, and the complement and coagulation cascades. This novel endophenotypic signature of gender-specific differences in whole serum confirmed and expanded the results of previous physiologic and pharmacologic studies exploring sexual dimorphism at the genomic and transcriptomic level in tissues and cells. Conclusively, the multifactorial and pleiotropic nature of human obesity exhibits sexual dimorphism in the circulating proteome of importance to clinical study design.

Assessing the contribution of 38 genetic loci to the risk of type 2 diabetes in the Saudi Arabian Population.

BACKGROUND: Previous genome-wide association studies have identified multiple type 2 diabetes (T2D) genetic risk loci in many populations. However, the contribution of these loci to T2D in the Middle Eastern populations with high T2D prevalence is unknown. METHODS: Here, we investigated the association of 38 T2D risk loci in the Saudi Arabian population (1166 patients with T2D and 1235 healthy controls), which has one of the world's highest prevalence of T2D. RESULTS: Eight common genetic variants showed a significant association with T2D in our study population. The effect sizes of these loci were comparable to those previously identified in other populations with the exception of HNF4A, which showed a trend for larger effect size in our study population (OR = 1·27) compared to that reported in South Asian populations (OR = 1·09; I(2) = 65·9). Analysis of risk allele scores (RASs) defined by the 8 loci showed that subjects in the top RAS quintile (n = 480) had 2·5-fold increase in disease risk compared to those in the bottom quintile (n = 480; P = 9·5 × 10(-12)). RASs were also associated with fasting glucose level (ß = 0·12; P = 2·2 × 10(-9)), but not with BMI (P = 0·19). Analysis of a subgroup of subjects with BMI≤30 resulted in two additional loci (SLC30A8; P = 0·03, HMG20A; P = 0·02) showing significant association with T2D. CONCLUSIONS: We have shown for the first time that variants at WFS1, JAZF1, SLC30A8, CDKN2A/B, TCF7L2, KCNQ1, HMG20A, HNF4A and DUSP9 are associated with T2D in the Saudi population. Our findings also suggest substantial overlap of T2D risk loci across many ethnic groups regardless of disease prevalence.

Maternal inheritance of circulating irisin in humans.

The recently discovered myokine irisin has been implicated in several observational studies as a potential therapeutic target for obesity-related diseases. However, no information is available as to the heritability of this hormone. The present study aims to fill this gap. A total of 120 families (n=254; 121 adults and 133 children) were included in the study taken from the Riyadh Biomarkers Research Program cohort. Information gathered include anthropometrics, and glycaemic, lipid and adipocytokine profiles. Irisin was measured using ELISA. Examining heritability between mother and offspring, the most significant heritable traits in sons included irisin (P=1.6×10(-5)), systolic blood pressure (P=3.6×10(-4)), total cholesterol (P=3.5×10(-7)) and LDL (low-density lipoprotein)-cholesterol (P=1.2×10(-6)). Heritable traits between mother and daughter again included irisin (P<0.002), as well as anthropometric associations such as waist (P<0.01) and hip (P<0.005) circumference and blood pressure (P<0.002); biochemically, principal associations were observed with HDL (high-density lipoprotein)-cholesterol (P<0.04) and TNF-α (tumour necrosis factor-α) (P<0.002). HDL-cholesterol was the single most significant predictor for irisin levels in adults, explaining 17% of the variance, whereas in children AngII (angiotensin II) was the most significant predictor of irisin levels, explaining 19% of the variance (P=0.003). Circulating irisin appears to be maternally inherited and is predicted by HDL-cholesterol in adults and AngII in children, both factors influenced by energy expenditure and regulation. Taken together, these findings suggest a significant role of irisin in energy-generating processes.

Molecular insights into the association of obesity with breast cancer risk: relevance to xenobiotic metabolism and CpG island methylation of tumor suppressor genes.

Obesity, genetic polymorphisms of xenobiotic metabolic pathway, hypermethylation of tumor suppressor genes, and hypomethylation of proapoptotic genes are known to be independent risk factors for breast cancer. The objective of this study is to evaluate the combined effect of these environmental, genetic, and epigenetic risk factors on the susceptibility to breast cancer. PCR-RFLP and multiplex PCR were used for the genetic analysis of six variants of xenobiotic metabolic pathway. Methylation-specific PCR was used for the epigenetic analysis of four genetic loci. Multifactor dimensionality reduction analysis revealed a significant interaction between the body mass index (BMI) and catechol-O-methyl transferase H108L variant alone or in combination with cytochrome P450 (CYP) 1A1m1 variant. Women with "Luminal A" breast cancer phenotype had higher BMI compared to other phenotypes and healthy controls. There was no association between the BMI and tumor grade. The post-menopausal obese women exhibited lower glutathione levels. BMI showed a positive association with the methylation of extracellular superoxide dismutase (r = 0.21, p < 0.05), Ras-association (RalGDS/AF-6) domain family member 1 (RASSF1A) (r = 0.31, p < 0.001), and breast cancer type 1 susceptibility protein (r = 0.19, p < 0.05); and inverse association with methylation of BNIP3 (r = -0.48, p < 0.0001). To conclude based on these results, obesity increases the breast cancer susceptibility by two possible mechanisms: (i) by interacting with xenobiotic genetic polymorphisms in inducing increased oxidative DNA damage and (ii) by altering the methylome of several tumor suppressor genes.

Induction of CYP1A1, CYP1A2, CYP1B1, increased oxidative stress and inflammation in the lung and liver tissues of rats exposed to incense smoke.

Incense smoke is increasingly being recognized as a potential environmental contaminant and is linked to malignant and non-malignant respiratory diseases. The detoxification of environmental contaminants including polycyclic aromatic hydrocarbons (PAHs) involves the induction of cytochrome P-450 family enzymes (CYPs) by PAHs. However, the detoxification of PAHs also results in the generation of reactive and unstable intermediary metabolites which are implicated in the oxidative stress, DNA damage, and inflammation. It is unclear whether CYPs are similarly induced by incense smoke, which incidentally contains substantial amounts of PAHs. Here, we examined the impact of long-term incense smoke exposure on the induction of CYPs in male Wister Albino rats. Incense smoke exposure significantly induced the expression of CYP1A1, CYP1A2, and CYP1B1 mRNAs in both lung and liver tissues. The extent of CYP1A1 and CYP1B1 induction was significantly higher in the liver compared to that in the lung, while that of CYP1A2 was greater in the lung than in liver. Incense smoke exposure also increased malondialdehyde and reduced glutathione levels in lung and liver tissues, and the catalase activity in the liver tissues to significant levels. Furthermore incense smoke exposure led to a marked increase in TNF-α and IL-4 levels. The data demonstrate for the first time the capacity of incense smoke to induce CYP1 family enzymes in the target and non-target tissues. Induction of CYPs increased oxidative stress and inflammation appear to be intimately linked to promote the carcinogenesis and health complications in people chronically exposed to incense smoke.

Does visceral adiposity index signify early metabolic risk in children and adolescents?: association with insulin resistance, adipokines, and subclinical inflammation.

BACKGROUND: Visceral adiposity index (VAI) is a novel gender-specific index based on waist circumference (WC), BMI, and lipid parameters. Although VAI does not actually estimate visceral adiposity, it accurately reflects visceral fat function and insulin resistance. This index has not been studied in children thus far. This study aims to fill this gap. METHODS: In a cohort of Saudi children and adolescents, anthropometric measurements and metabolic/hormonal profile were obtained. RESULTS: A total of 543 subjects, 292 of whom were boys, were included (mean age: 11.9 ± 3.3 y; BMI: 19.8 ± 5.6 kg/m(2)). In all subjects, VAI was inferior to BMI and WC regarding its correlations with adiponectin, leptin, insulin resistance (homeostasis model of assessment-insulin resistance (HOMA-IR)), C-reactive protein (CRP) level, and systolic blood pressure, but it exhibited a stronger association with glucose in boys (r = 0.23; P < 0.01). In stepwise multivariate analyses, only BMI was consistent as an independent predictor of adiponectin, leptin, HOMA-IR, and CRP. VAI was the only index independently associated with glucose. CONCLUSION: Although VAI is related to glucose in children, it seems to be inferior to BMI in terms of association with insulin resistance, adipokines, and subclinical inflammation. Until specific studies can be performed in children, VAI should be extrapolated with caution in this age range.

Vitamin D receptor gene polymorphisms and HLA DRB1*04 cosegregation in Saudi type 2 diabetes patients.

The vitamin D receptor (VDR) gene has been involved in the modulation of susceptibility to inflammatory and autoimmune conditions, and could play a role in the pathogenesis of type 2 diabetes mellitus (T2DM). Susceptibility to T2DM was recently also suggested to associate with HLA alleles. We evaluated possible correlations between VDR polymorphisms, HLA alleles, and risk for development of T2DM by analyzing 627 individuals (368 T2DM patients and 259 healthy control subjects) part of a well-characterized cohort followed in Riyadh, Kingdom of Saudi Arabia. Genomic DNA was genotyped for the VDR gene single nucleotide polymorphisms of Fok-1, Taq-1, ApaI, and Bsm-I. Analyses were run by allelic discrimination real-time PCR. HLA genotyping was performed as well by PCR using sequence-specific primers, whereas cytokine production was evaluated by FACS. Results showed T2DM to be significantly associated with the VDR Taq1 (rs731236-AG) and Bsm-I (rs1544410-CT) genotypes, and the VDR rs1544410-T allele. Cosegregations resulting in significant increases of T2DM odds ratio were detected between Taq1 and Bsm-I VDR polymorphisms and HLA DRB1*04. Notably, the VDR polymorphisms observed to be more frequent in T2DM patients correlated with increased VDR expression and IL-12 production, as well as with metabolic parameters of susceptibility to T2DM, including serum cholesterol and high-density lipoprotein levels. VDR polymorphisms are present in T2DM, and correlate with HLA DRB1*04 and with immunologic and metabolic parameters; results from this study add T2DM to the list of diseases that are likely modulated by an HLA/VDR interaction.

Association between type 2 diabetes mellitus-related SNP variants and obesity traits in a Saudi population.

Obesity, commonly measured as body mass index (BMI), has been on a rapid rise around the world and is an underlying cause of several chronic non-communicable diseases, including type 2 diabetes mellitus (T2DM). In addition to the environmental factors, genetic factors may also contribute to the ongoing obesity epidemic in Saudi Arabia. This study investigated the association between variants of 36 previously established T2DM SNPs and obesity phenotypes in a population of Saudi subjects. Study subjects consisted of 975 obese (BMI: ≥30), 825 overweight (25-30) and 423 lean controls (18-25) and of these 927 had a history of T2DM. Subjects were genotyped for 36 SNPs, which have been previously proved to be T2DM linked, using the KASPar method and the means of BMI and waist circumference (WC) corresponding to each of the genotypes were compared by additive, recessive and dominant genetic models. Five and seven of 36 T2DM-related SNPs were significantly associated with the BMI and WC, respectively. Variants of SNPs rs7903146, rs1552224 and rs11642841 in the control group and rs7903146 in T2DM group showed significant association with both BMI and WC. Variant of SNP rs10440833 was significantly associated with BMI in T2DM group of both males [OR = 1.8 (1.0, 3.3); P = 0.04] and females [OR = 2.0 (1.0, 3.9); P = 0.04]. Genetic risk scores explained 19 and 14% of WC and hip size variance in this population. Variants of a number of established T2DM related SNPs were associated with obesity phenotypes and may be significant hereditary factors in the pathogenesis of T2DM.

Gender-dependent associations between socioeconomic status and metabolic syndrome: a cross-sectional study in the adult Saudi population.

BACKGROUND: To determine the gender-dependent association of socio-economic status variables with the prevalence of metabolic syndrome (MetS) in the adult Saudi population. METHODS: A total of 9164 adult Saudis (aged 18-70 years) were included in this cross-sectional study. Marital status, income, education, and occupation were used as socio-economic indicators while behavioral factor like physical exercise was also taken into account. MetS was defined using the criteria based from the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III). RESULTS: In males, the odds ratio (OR) of harboring MetS was higher in married [OR1.6 (Confidence Interval (CI) 1.1, 2.4); p < 0.03], and high income class [OR 2.3(CI 1.5, 3.5); p < 0.001] and lowest in retired and unemployed individuals [1.4(1.0, 1.9); p < 0.04, 0.61(0.45, 0.82); p < 0.001] respectively. In females, MetS was inversely related to high income [OR 0.70 (CI 0.46, 1.1); p < 0.09] and education level [OR 0.38 (CI 0.26, 0.56); p < 0.001], and was significantly higher in the unemployed class [OR 1.6 (CI 1.2, 2.2); p < 0.004]. CONCLUSIONS: The prevalence of MetS is significantly high among retired, married and high-earning Saudi males while in females, high earners and high education seem to confer a protective effect against MetS.

Stress and cardiometabolic manifestations among Saudi students entering universities: a cross-sectional observational study.

BACKGROUND: In this observational study, we aimed to see whether transition in Saudi students entering university life could be a breeding stage for cardiometabolic risk factor emergence and clustering. METHODS: A total of 1878 apparently healthy Saudi students of the Preparatory Year, King Saud University, Riyadh, KSA (1112 men and 766 women) spanning 2 academic years were included. They were divided into 2 groups based on the validated perceived stress test (PST). Anthropometrics were obtained and fasting blood samples were collected for measurement of fasting blood glucose and a lipid profile. RESULTS: PST score (>27) considered indicative of stress was noted in 44.4% of students. The prevalence of this score was higher in women than in men (49.7% versus 40.7%). The prevalence of obesity, hypertension and dyslipidemia was significantly higher in men than women (p < 0.01), and this was even more apparent among stressed men, who had a significantly higher prevalence of all the above cardiometabolic factors than the non-stressed ones (p < 0.01). CONCLUSION: Perceived stress is alarmingly high among Saudi students entering universities. This study sheds light on the social responsibility of universities in promoting a healthy lifestyle, particularly in this age group, when exposure to different kinds of stressors may result in body weight and metabolic changes.

Lower vitamin D status is more common among Saudi adults with diabetes mellitus type 1 than in non-diabetics.

BACKGROUND: Vitamin D deficiency is an increasingly recognized comorbidity in patients with type 1 diabetes mellitus (DMT1), suggesting that vitamin D deficiency might play a role in DMT1. We aimed to determine and compare the vitamin D status of Saudi adults with and without DMT1. METHODS: A total of 60 Saudi adults with DMT1 from the Diabetes Clinics and 60 non-DM, healthy controls were included in the study. The mean age for those with DMT1 was 25.9 ± 16.1 years versus 36.7 ± 3.6 years among the controls. We measured serum 25-hydroxy vitamin D (25OHD), calcium, cholesterol, blood glucose, HDL, and triglycerides and compared the results between the DMT1 group and control subjects. RESULTS: Both the DMT1 and healthy groups had vitamin D deficiency. The mean levels of 25OHD were significantly lower in the DMT1 adults than in the controls (28.1 ± 1.4 nmol/L versus 33.4 ± 1.6 nmol/L). In the DMT1 adults, 66.7% were mildly, 31.7% moderately, and 3.3% severely vitamin D deficient as compared with 41.7% (mildly), 31.7% (moderately), and 5% (severely) in the control group. Overall, 100% of the DMT1 adults and 78% of the healthy children were vitamin D deficient. CONCLUSION: The prevalence of vitamin D deficiency among DMT1 adults was relatively high. Therefore, screening for vitamin D deficiency and supplementation for this population should be warranted.