ASSOCIATION OF GENOTYPES AND HAPLOTYPES OF TUMOUR NECROSIS FACTOR –ALPHA (TNF-α) WITH OVERWEIGHT/OBESITY-RELATED PHENOTYPES IN MALAYSIAN POPULATION

Abstract

Background: Obesity is classified as low-grade chronic inflammatory disease and genetic predisposition may play a role in the susceptibility to obesity development. Previous studies have shown that pro-inflammatory cytokine, TNF-α promoter region polymorphism was associated with overweight/obesity in various population. Therefore, this study aims to investigate the association of three single nucleotide polymorphisms of TNF-α (G-308A, C-863A and G-238A) and their haplotypes with the risk of overweight/ obesity in Malaysian population. Methods: Classification of overweight/obesity followed the Malaysian Clinical Practice Guideline of Obesity (2004). Polymorphisms of TNF-α (G-308A, C-863A and G-238A) were evaluated on 105 overweight/obese subjects and 100 non-overweight/ non-obese subjects as controls through tetra-arms PCR. Chi square and logistic regression analysis were done using SPSS software while haplotype and linkage disequilibrium analysis were done using HaploView 4.2 software. Results: The rare A alleles of TNF-α G-308A, C-863A and G-238A did not occur more frequently in overweight/obese individual as compared to controls. Similar results were obtained in allele frequency comparison among Chinese and Korean population for G-308A, G-238A and C-863A polymorphism. Although weak linkage disequilibrium was found between the markers tested, there were six haplotypes occurred in more than 1% of the population, with 308G/-863C/-238G as the most frequent haplotypes. Conclusion: This study recorded no association of TNF-α G-308A, C-863A and G-238A with two overweight/obesity phenotypes, BMI and WHR. Further studies with larger cohort and other obesity-related phenotypes are required to investigate the possible association of TNF-a polymorphism with overweight/obesity in Malaysian population.