Inter-Ethnic Variations in Association of TNF-Alpha G308a Single Nucleotide Polymorphism with Type 2 Diabetes Mellitus - A Review

Abstract

According to World Health Organization, the prevalence of diabetes mellitus (DM) is on the rise. Tissue necrosis factor- alpha (TNF-α) is one of the inflammatory markers which play role in the pathogenesis of DM. Single nucleotide polymorphism (SNP) at 308G/A has been reported to be associated with type 2 DM. Frequency of TNF-α G308A polymorphism was determined in different ethnic groups and is found to be highly variable. Limited number of studies reported a positive association between type 2 DM and TNF-α SNP and many studies; including meta-analyses failed to find such association. TNF-α G308A polymorphism has been found to be associated with insulin resistance and BMI, although these findings are challenged by many studies. The probable explanation of higher BMI is the association of presence of TNF- α G308A polymorphism with higher rates of lipid synthesis, and suppression of FFA levels in obese persons. There is no single explanation for such highly variable results in different ethnic groups. Presence of yet unidentified gene polymorphism in linkage disequilibrium with TNF-α gene polymorphism could be responsible. The different results can also be contributed to the fact that the study groups differ in age, gender distribution, age of onset of disease, life style, degree of obesity and glucose tolerance. Comprehensive genetic studies of whole TNF-alpha promoter area are required to be done in large population samples in different ethnic groups. Polymorphisms are usually co-related in a complex manner and are co-inherited and conclusions are difficult to be drawn on small sample size.