Deep intronic 9q21.11 polymorphism contributes to atopic dermatitis risk through methylation regulated expression of tight junction protein 2.

BACKGROUND AND OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory itchy skin condition. Genomic- and epigenetic wide association studies provide insights into the genetic susceptibility and potential underlying disease pathogenesis. This study sought to functionally characterise an AD-associated single nucleotide polymorphism (SNP) located deep intronic of the tight junction protein 2 (TJP2) gene (9q21.11 locus), identified through a genome-wide association study (GWAS). METHODS: The association between the 9q21.11 locus (rs7872806) and AD was identified through a GWAS of 956 cases and 723 controls. TJP2 expression in peripheral blood mononuclear cells (PBMCs) was assessed against the rs7872806 genotypes. Allele-specific methylation was evaluated at CpG sites 10kb up- and down-stream of the 9q21.11 locus. Effects of DNA methylation on TJP2 expression was validated via in vitro methylation and 5-aza-2'-deoxycytidine-induced transcriptional activation studies. Trans-epidermal water loss measurements were used to determine skin barrier function. RESULTS: The major allele of rs7872806 was determined to increase AD risk by 2.64-fold (adjusted p-value=2.40 x 10-18, OR=0.38), associated with increased methylation levels at cg13920460 site (p<0.001) and lower TJP2 expression in PBMCs (Pearson's p=1.09 x 10-6, Pearson's R=-0.313, p<0.001). Methylation inhibition by 5-aza-2'-deoxycytidine increased TJP2 promoter activity by up to 85%. Elimination of the cg13920460 methylation site increased expression by approximately 25%. The rs7872806 major allele was also found to be associated with increased trans-epidermal water loss (p<0.001). CONCLUSION: Epigenetic influence at CpG site cg13920460 is associated with rs7872806 located deep intronic at 9q21.11. The SNP confers susceptibility to AD through altering TJP2 expression and promoting trans-epidermal water loss.

Associated Factors of Sleep Quality and Behavior among Students of Two Tertiary Institutions in Northern Malaysia.

The objective of the study was to investigate the associated factors of sleep quality and behavior among Malaysian tertiary students. The response rate to the questionnaire study was 41.0%. 1,118 students (M = 486, F = 632; mean age = 20.06 ± 1.53 years) were recruited from Universiti and Kolej Tunku Abdul Rahman (Perak campuses) who completed a sleep quality and behavior questionnaire based on Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Horne-Ostberg Morningness-Eveningness Scale (MES) and craving of high-calorie foods. Results showed that students had the following sleeping habits - bed time = 2.41 a.m. ± 3.35 hr, rise time = 9.00 a.m. ± 1.76 hr, sleep latency = 16.65 ± 14.30 min and sleep duration = 7.31 ± 1.45 hr. 32.9% of the students were defined as poor quality sleepers, 30.6% suffering excessive daytime sleepiness (EDS) and 81.6% were categorized as individuals with 'definitely eveningness', defined as people who are definitely most alert in the late evening hours and prefer to go to bed late. There were no significant gender differences in sleep quality, 'chronotype' and EDS. Although there was no association of sleep quality and EDS with cumulative Grade Point Average (cGPA) and class skipping, EDS was associated with the tendency to fall asleep in class. Body Mass Index (BMI) was not associated with total sleep, PSQI, ESS and MES scores. Meanwhile, high-calorie food craving was associated with sleep duration, PSQI and ESS, but not MES. In conclusion, poor sleep behavior among Malaysian tertiary students in this study was not associated with gender, academic performance and BMI, but was associated with craving of high-calorie foods instead.

Prevalence of melanocortin receptor 4 (MC4R) V103I gene variant and its association with obesity among the Kampar Health Clinic cohort, Perak, Malaysia.

This study investigated the prevalence of the Melanocortin receptor 4 (MC4R) V1031 gene variant and its association with obesity among a cohort of 254 patients (101 males; 118 obese) attending the Kampar Health Clinic. Genotyping revealed the mutated I allele frequency of 0.02, no homozygous mutated (II), and similar distribution of V and I alleles across BMI groups, genders and ethnic groups. No significant difference was found for the means of anthropometric measurements between alleles. Prevalence of this gene variant among the Malaysian cohort was similar with previous populations (2-4% of mutated allele carrier), but was not associated with obesity.

Plasma total antioxidant capacity (TAC) in obese Malaysian subjects.

INTRODUCTION: There is a pressing need to better understand the complex biochemical pathways that lead to the pathogenesis of obesity. Increased oxidative stress and decreased antioxidant capacity have been identified to be associated with obesity. Therefore, the objectives of this study were to determine the plasma total antioxidant capacity (TAC) levels of Malaysian subjects and to evaluate its potential association with obesity and related anthropometric measurements. METHODS: Plasma TAC of 362 multi-ethnic Malaysian subjects from the Kampar Health Clinic (138 males, 224 females; 124 ethnic Malays, 152 Chinese, 86 Indians; 192 non-obese, 170 obese) was measured using Trolox equivalent antioxidant capacity (TEAC) 96-well plate assay. RESULTS: Plasma TAC was significantly lower in obese subjects (M +/- SE = 292 +/- 10.4 micromol/L) compared to non-obese subjects (397 +/- 8.58 micromol/L), whereas it was significantly higher in males and those in the 21-30 age group. Those with salty food preference and practising a strict vegetarian diet also had significantly higher plasma TAC. However, no association was found for other dietary habits (coffee intake) and lifestyle factors (physical activity, smoking). Plasma TAC was also significantly negatively correlated with diastolic blood pressure, waist and hip circumferences, weight, body mass index, total body fat, % subcutaneous fat, visceral fat level, resting metabolism and % skeletal muscle. CONCLUSION: Plasma TAC was found to be associated with obesity, strict vegetarian practice, salty food preference and all obesity anthropometric indicators, except systolic blood pressure and pulse rate. Obese people have decreased plasma TAC indicating a compromised systemic antioxidant defence and increased oxidative stress.

No association of peptide tyrosine-tyrosine (PYY) gene R72T variant with obesity in the Kampar Health Clinic cohort, Malaysia.

INTRODUCTION: Peptide Tyrosine-Tyrosine (PYY) is a 36-amino acid peptide hormone released post-prandially from the endocrine cells in the intestinal tract to suppress pancreatic secretions and eventually reduce appetite. The R72T variant in the PYY gene (rs1058046) has been associated with increased susceptibility to obesity. Therefore, the objective of this study was to investigate the association of this variant with obesity and its related anthropometric measurements among the Kampar Health Clinic cohort, Malaysia. METHODOLOGY: A total of 197 (78 males, 119 females; 98 non-obese, 99 obese) subjects were recruited by convenience sampling and anthropometric measurements were taken. Genotyping was performed using StuI Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP), revealing 61 RR, 94 RT and 42 TT subjects. RESULTS: Most of the obese subjects had the RT genotype (50.5%), while only 18.2% were TT. PYY R72T genotypes and alleles had no association with obesity (p = 0.535; 0.074, respectively), gender (p = 0.767; p = 0.100, respectively) but were associated with ethnicity (p = 0.003; p = 0.002, respectively). Among the 13 anthropometric measurements taken, significant difference was only found in Waist Circumference (WC) and Visceral Fat Level (VFL) among the alleles, suggesting that subjects with T allele will have an increment of 1.82 cm in WC and 1.32% in VFL. CONCLUSION: The R72T variant in PYY gene was not associated with obesity and most of its related anthropometric measurements. This suggests that other genes and/or environmental factors like dietary habits and lifestyle factors may be the contributors of obesity.