Tumor necrosis factor-alpha gene polymorphisms and complex disorders: A study among mendelian population with East Asian Ancestry

Abstract

Background and Objectives: Tumor necrosis factor-alpha (TNF-α)-238G/A and -308G/A single-nucleotide polymorphisms (SNPs) in the promoter region of the gene have been implicated in numerous diseases. The present study aims to investigate the frequency of two TNF-α polymorphisms among Mendelian population of India and to assess their association with various cardiovascular risk variables and outcomes (hypertension [HTN], metabolic syndrome [MetS], and type 2 diabetes mellitus). Materials and Methods: A total of 1142 unrelated individuals aged 35–75 years belonging to Meitei community of Manipur were included in the study. Height, weight, waist and hip circumferences, blood pressures (systolic and diastolic), and lipid profile were measured. Polymerase chain reaction was done using standard protocols. Further, HTN, MetS, diabetic, and healthy individuals were identified, and a nested case–control study design was formulated. Results: The mutant allele frequency was found to be similar (4%) for both the polymorphisms among the Meiteis of Manipur. No mutant homozygote of TNF-α-308G/A polymorphism was observed. No significant risk of the two polymorphisms was found with any of the disease groups in nested case–control analysis. However, TNF-α-308G/A polymorphism, but not TNF-α-238G/A polymorphism, was found to be associated with total cholesterol (TC), triglyceride (TG), and very-low-density lipoprotein (VLDL) in overall population only with TG and VLDL among the HTN cases. Conclusion: The association of TNF-α-308A allele with metabolic risk factors such as TC, TG, and VLDL suggests that though it may not increase the development of any of the diseases considered in the present study, it could possibly enhance the risk of human metabolic disorder. The absence of mutant homozygote among cases is suggestive of lethality of TNF-α-308A allele in double dose coupled with other environmental factors or in the presence of haplotype pairing with TNF-α-238A allele.

Keywords

• Complex disorders
• Mendelian population
• polymorphism