Factors Associated With Obesity and Abdominal Obesity Among Malaysian Older Adults.

Obesity is a rising concern globally. This study investigated the prevalence and factors associated with obesity and abdominal obesity (AO) among 5613 Malaysians aged 40 years and older via computer-assisted personal interviewing and anthropometric measurements. Obesity and AO prevalence were 37.8% and 63.1%, respectively. Significant associations were observed between: obesity with higher risk in patients aged between 40 and 49 years, Indians, females, income ≥RM 2000, and health status, and AO with higher risk in patients aged between 50 and 59 years, Indians, females, never married, income ≥RM 2000, and vigorous physical activity. Hence, age, sex, income, and ethnicity are associated with both obesity and AO. Promoting healthy body mass index and waist circumference is essential for healthy ageing.

Interleukin-6 gene variants are associated with reduced risk of chronicity in hepatitis B virus infection in a Malaysian population.

Interleukin-6 (IL-6) is a cytokine with a critical role in regulating the immune response to infectious disease. Studies have indicated that polymorphisms in the IL-6 gene may be linked to hepatitis B virus (HBV) infection. The purpose of the present study was to examine the association among IL-6 SNPs and haplotypes with HBV infection risk in a Malaysian population. A total of 1,246 Malaysian subjects with and without chronic hepatitis B were recruited for this study. Three IL-6 polymorphisms (rs2069837, rs1800796 and rs2066992) were genotyped using a Sequenom MassARRAY® platform. The results suggested that GC and CC genotypes of rs1800796 as well as GT and TT genotypes of rs2066992 were associated with protection against HBV infection (P<0.001). Furthermore, haplotypes GG and CT exhibited a significant association with protection against HBV (P=0.003 and =0.005, respectively); and haplotypes GG and CT exhibited a significant association with clearance of HBV infection (P=0.035 and =0.037, respectively). The present study indicates that two IL-6 SNPs (rs1800796 and rs2066992) are associated with clearance of chronic HBV or protection against HBV infection at allelic, genotypic and haplotypic levels.

Circulating microRNA as a marker for predicting liver disease progression in patients with chronic hepatitis B.

INTRODUCTION: Hepatitis B virus (HBV) constitutes an important risk factor for cirrhosis and hepatocellular carcinoma (HCC). The link between circulating microRNAs and HBV has been previously reported, although not as a marker of liver disease progression in chronic hepatitis B (CHB). The aim of this study was to characterize miRNA expression profiles between CHB with and without cirrhosis or HCC. METHODS:: A total of 12 subjects were recruited in this study. We employed an Affymetrix Gene Chip miRNA 3.0 Array to provide universal miRNA coverage. We compared microRNA expression profiles between CHB with and without cirrhosis/HCC to discover possible prognostic markers associated with the progression of CHB. RESULTS:: Our results indicated 8 differently expressed microRNAs, of which miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, and miRNA-3200 were up-regulated, whereas miRNA-182 and miRNA-4485 were down-regulated in patients with CHB who progressed to cirrhosis/HCC as compared to those without progression. CONCLUSIONS:: We demonstrated the differential expression of miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, miRNA-3200, miRNA-182, and miRNA-4485 between patients with HBV without cirrhosis/HCC and those who had progressed to these more severe conditions. These miRNAs may serve as novel and non-invasive prognostic markers for early detection of CHB-infected patients who are at risk of progression to cirrhosis and/or HCC.

Circulating microRNA as a marker for predicting liver disease progression in patients with chronic hepatitis B

Abstract INTRODUCTION Hepatitis B virus (HBV) constitutes an important risk factor for cirrhosis and hepatocellular carcinoma (HCC). The link between circulating microRNAs and HBV has been previously reported, although not as a marker of liver disease progression in chronic hepatitis B (CHB). The aim of this study was to characterize miRNA expression profiles between CHB with and without cirrhosis or HCC. METHODS: A total of 12 subjects were recruited in this study. We employed an Affymetrix Gene Chip miRNA 3.0 Array to provide universal miRNA coverage. We compared microRNA expression profiles between CHB with and without cirrhosis/HCC to discover possible prognostic markers associated with the progression of CHB. RESULTS: Our results indicated 8 differently expressed microRNAs, of which miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, and miRNA-3200 were up-regulated, whereas miRNA-182 and miRNA-4485 were down-regulated in patients with CHB who progressed to cirrhosis/HCC as compared to those without progression. CONCLUSIONS: We demonstrated the differential expression of miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, miRNA-3200, miRNA-182, and miRNA-4485 between patients with HBV without cirrhosis/HCC and those who had progressed to these more severe conditions. These miRNAs may serve as novel and non-invasive prognostic markers for early detection of CHB-infected patients who are at risk of progression to cirrhosis and/or HCC.

Interleukin 1 receptor type 2 gene polymorphism is associated with reduced risk of preterm birth.

OBJECTIVE: Interleukin 1 receptor type 2 (IL1R2) regulates the inflammatory pathway that results in preterm delivery. We aim to investigate the impact of IL1R2 gene polymorphisms on the risk of preterm delivery. METHOD: A total of 664 women with spontaneous preterm and term deliveries were genotyped for IL1R2 gene polymorphisms (rs2072476A/G, rs2071008G/T, rs2072474C/T) using Sequenom MassARRAY platform. RESULTS: Ethnic-specific analysis revealed a significant association between the G allele of IL1R2 rs2072476 polymorphism and reduced risk of PTB in the Indian ethnic subgroup (OR: 3.7, 95% CI: 1.3-11.3, p = 0.017). The odds of G allele occurring among Indian women with term delivery (>37 weeks) was three times higher than those with preterm delivery (<37 weeks). Genotype analysis showed a significant association between the GG genotype of IL1R2 rs2072476 polymorphism and term delivery in the Indian women. CONCLUSION: This study shows disparity in the occurrence of preterm birth due to the differences in the genotype of the women. Particularly, Indian women with the minor allele of IL1R2 rs2072476 polymorphisms were more likely to deliver at term (>37 weeks). These findings suggest the possible influence of maternal IL1R2 gene polymorphism on the risk of preterm delivery.

Progesterone Receptor (PGR) gene polymorphism is associated with susceptibility to preterm birth.

BACKGROUND: Preterm birth (PTB) is the major cause of death in newborn and the second major cause of death in children less than 5 years old worldwide. Genetic polymorphism has been implicated as a factor for the occurrence of preterm birth. The aim of this study is to evaluate whether polymorphism in the progesterone receptor (PGR) is associated with susceptibility to preterm birth. METHODS: A total of 135 women with preterm and 532 women with term deliveries were genotyped for PGR gene polymorphisms (rs660149, rs471767, rs10895068) using Sequenom MassARRAY platform. RESULTS: The G allele of PGR rs660149 polymorphism was significantly associated with susceptibility to PTB in the Malay women. The odds of G allele occurring among Malay women with preterm delivery was twice that of Malay women with term delivery (OR 2.3, 95 % CI (1.2-4.5, P = 0.011). Alternatively, no significant association was observed between PGR rs660149 polymorphisms and susceptibility to PTB in Chinese and Indian women. CONCLUSIONS: This study shows that variability in the occurrence of PTB across ethnicities in Malaysia is partly due to differences in genetic background. We therefore suggest that in addition to life style and environmental factors, genetic factor should be greatly considered in this population. Prior information on the genetic composition of women may help in the identification and management of women at risk of preterm birth complication.

Polymorphisms of the resistin gene and their association with obesity and resistin levels in Malaysian Malays.

Single nucleotide polymorphisms (SNP) in the resistin gene (RETN) are linked to obesity and resistin levels in various populations. However, results have been inconsistent. This study aimed to investigate association between polymorphisms in the resistin gene with obesity in a homogenous Malaysian Malay population. This study is also aimed to determine association between resistin levels with certain SNPs and haplotypes of RETN. A total of 631 Malaysian Malay subjects were included in this study and genotyping was carried out using Sequenom MassARRAY. There was no significant difference found in both allelic and genotype frequencies of each of the RETN SNPs between the obese and non-obese groups after Bonferroni correction. RETN rs34861192 and rs3219175 SNPs were significantly associated with log-resistin levels. The GG genotype carriers are found to have higher levels of log-resistin compared to A allele carriers. The RETN haplotypes (CAG, CGA and GA) were significantly associated with resistin levels. However, the haplotypes of the RETN gene were not associated with obesity. Resistin levels were not correlated to metabolic parameters such as body weight, waist circumference, body mass index, and lipid parameters. RETN SNPs and haplotypes are of apparent functional importance in the regulation of resistin levels but are not correlated with obesity and related markers.

Obesity and genomics: role of technology in unraveling the complex genetic architecture of obesity.

Obesity is a complex and multifactorial disease that occurs as a result of the interaction between "obesogenic" environmental factors and genetic components. Although the genetic component of obesity is clear from the heritability studies, the genetic basis remains largely elusive. Successes have been achieved in identifying the causal genes for monogenic obesity using animal models and linkage studies, but these approaches are not fruitful for polygenic obesity. The developments of genome-wide association approach have brought breakthrough discovery of genetic variants for polygenic obesity where tens of new susceptibility loci were identified. However, the common SNPs only accounted for a proportion of heritability. The arrival of NGS technologies and completion of 1000 Genomes Project have brought other new methods to dissect the genetic architecture of obesity, for example, the use of exome genotyping arrays and deep sequencing of candidate loci identified from GWAS to study rare variants. In this review, we summarize and discuss the developments of these genetic approaches in human obesity.

Genetic polymorphisms in the androgen metabolism pathway and risk of prostate cancer in low incidence Malaysian ethnic groups.

Androgens are involved in prostate cancer (PCa) cell growth. Genes involved in androgen metabolism mediate key steps in sex steroid metabolism. This study attempted to investigate whether single nucleotide polymorphisms (SNPs) in the androgen metabolism pathway are associated with PCa risk in low incidence Asian ethnic groups. We genotyped 172 Malaysian subjects for cytochrome P450 family 17 (CYP17A1), steroid-5-alpha-reductase, polypeptide 1 and 2 (SRD5A1 and SRD5A2), and insulin-like growth factor 1 (IGF-1) genes of the androgen metabolism pathway and assessed the testosterone, dihydrotestosterone and IGF-1 levels. SNPs in the CYP17A1, SRD5A1, SRD5A2, and IGF-1 genes were genotyped using real-time polymerase chain reaction. Although we did not find significant association between SNPs analysed in this study with PCa risk, we observed however, significant association between androgen levels and the IGF-1 and several SNPs. Men carrying the GG genotype for SNP rs1004467 (CYP17A1) had significantly elevated testosterone (P = 0.012) and dihydrotestosterone (DHT) levels (P = 0.024) as compared to carriers of the A allele. The rs518673 of the SRD5A1 was associated with prostate specific antigen (PSA) levels. Our findings suggest CYP17A1 rs1004467 SNP is associated with testosterone and DHT levels indicating the importance of this gene in influencing androgen levels in the circulatory system of PCa patients, hence could be used as a potential marker in PCa assessment.

Gender-dependent association of a ß(2)-adrenergic gene variant with obesity parameters in Malaysian Malays.

Recent findings have shown that the rs1042714 (Gln27Glu) single-nucleotide polymorphism (SNP) on the ß2-adrenoceptor gene may predispose to obesity. The findings from other studies carried on different populations, however, have been inconsistent. The authors investigated the association between the rs1042714 SNP with obesity-related parameters. DNA of 672 Malaysian Malays was analyzed using real-time polymerase chain reaction. Univariate and multivariate linear regression analyses revealed significant associations between rs1042714 and diastolic blood pressure in the pooled Malaysian Malay subjects under additive and recessive models. After gender stratification, however, a significant association was found between the rs1042714 and triglyceride and the rs1042714 and log-transformed high-density lipoprotein cholesterol levels in Malaysian Malay men. No significant association was found between the SNP and log-transformed body mass index. This polymorphism may have an important role in the development of obesity-related traits in Malaysian Malays. Gender is an effect modifier for the effect of the rs1042714 polymorphism on obesity-related traits in Malaysian Malays.

Association of ADIPOQ gene with obesity and adiponectin levels in Malaysian Malays.

Studies have shown that single-nucleotide polymorphisms (SNPs) on the ADIPOQ gene have been linked with obesity and with adiponectin levels in various populations. Here, we aimed to investigate the association of ADIPOQ rs17366568 and rs3774261 SNPs with obesity and with adiponectin levels in Malaysian Malays. Obesity parameters and adiponectin levels were measured in 574 subjects. Genotyping was performed using real-time polymerase chain reaction and Sequenom MassARRAY. A significant genotypic association was observed between ADIPOQ rs17366568 and obesity. The frequencies of AG and AA genotypes were significantly higher in the obese group (11%) than in the non-obese group (5%) (P=0.024). The odds of A alleles occurring among the obese group were twice those among the non-obese group (odds ratio 2.15; 95% confidence interval 1.13-4.09). However, no significant association was found between allelic frequencies of ADIPOQ rs17366568 and obesity after Bonferroni correction (P>0.025) or between ADIPOQ rs3774261 and obesity both at allelic and genotypic levels. ADIPOQ SNPs were not significantly associated with log-adiponectin levels. GA, GG, and AG haplotypes of the ADIPOQ gene were not associated with obesity. We confirmed the previously reported association of ADIPOQ rs17366568 with the risk of obesity. ADIPOQ SNPs are not important modulators of adiponectin levels in this population.

Association of melanocortin-4 receptor gene polymorphisms with obesity-related parameters in Malaysian Malays.

BACKGROUND: Melanocortin-4 receptor (MC4R) is an important regulator of body weight and energy intake. Genetic polymorphisms of the MC4R gene have been found to be linked to obesity in many recent studies across the globe. AIM: This study aimed to examine the effects of MC4R polymorphisms on obesity parameters, Linkage disequilibrium (LD) pattern and haplotypes in Malaysian Malays. METHODS: The study subjects were 652 Malaysian Malays. Genomic DNA was extracted from buccal swabs. Genotyping was performed using Sequenom MassARRAY® iPLEX platform. Anthropometric and blood lipid profiles were measured. RESULTS: MC4R rs571312 SNP was associated with logBMI (p = 0.008) and systolic blood pressure (p = 0.005), while MC4R rs2229616 SNP was associated with total cholesterol (TC) levels (p = 0.016). The MC4R rs7227255 SNP did not show any association with obesity parameters. CONCLUSIONS: The strength of LD of the MC4R gene region is low and the haplotypes were not associated with obesity in Malaysian Malays.