Association of ADIPOQ C-11377G (rs266729), TNF-α αG-308A(rs1800629) and TNF-α αG-238A(rs361525) Single Nucleotide Polymorphisms with Type 2 Diabetes Mellitus in Pakistani Population.

Abstract

To determine the frequencies of adiponectin (ADIPOQ) C-11377G, tumor necrosis factor-alpha (TNF-α) G-308A and TNF-αG-238Asingle nucleotide polymorphisms (SNP) and their association with serum levels in Pakistani T2DM and healthy population. Case control study. Military Hospital, Rawalpindi, Army Medical College and Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan, from June 2012 till 2014. Cases (n=539) and controls (n=250) comprising of T2DM and healthy subjects, respectively, belonging to Pakistani Punjabi Rajput ethnicity were genotyped for SNPs. Serum adiponectin, TNF-α, insulin, blood sugar fasting (BSF), lipid profile, body mass index (BMI), and insulin resistance (IR) was determined and correlated with genotypes. Serum TNF-αwas significantly higher and adiponectin was lower in T2DM than healthy controls (p < 0.003 and 0.0001, respectively, Mann-Whitney U-test). The frequency of ADIPOQ CC, GC and GG was 340 (63.1%), 167 (31%) and 32 (5.9%) in T2DM patients. ADIPOQ -11377 SNPwas not significantly associated with T2DM [OR = 1.116 (95% CI 0.811.53), p = 0.27- Fisher's exact test]. Genotypes deviated from Hardy-Weinberg equilibrium. Minor alleles of TNF-αG-308A and TNF-αG-238Awere not found in either groups. Frequency of ADIPOQ -11377 risk allele is low and does not functionally affect the serum adiponectin levels; hence, ADIPOQ C-11377G SNPis not a risk factor for T2DM in Pakistani Punjabi Rajput patients. Moreover, TNF-αG-308A and TNF-αG-238ASNPs are not prevalent in this ethnic group.