A Haplotype at Adiponectin Locus: Relevance with Obesity and Type 2 Diabetes

Abstract

Background: Adiponectin is an anti-inflammatory insulin sensitizing adipokine. Association studies between adiponectin (ADIPOQ) gene single nucleotide polymorphisms (SNPs) and type 2 diabetes (T2D) have been reported earlier. However, results are ambiguous due to apparent contradictions. Hence, we aimed to investigate 1) the association between ADIPOQ SNPs: 11377C/G (rs266729), +10211T/G (rs17846866), +45T/G (rs2241766) and +276G/T (rs1501299), and the risk towards T2D in one precise cohort 2) genotype-phenotype association of these SNPs with various biochemical parameters like lipid profile, plasma ratio of high molecular weight (HMW) adiponectin to total adiponectin levels, and risk towards obesity and T2D. Methods: 475 diabetic patients and 493 ethnically age and sex-matched healthy controls were recruited for this study. 3mL blood was collected and plasma was separated for lipid profile and adiponectin estimation. Genomic DNA was isolated from PBMCs and was subjected to PCR-RFLP for genotyping. The ratio of plasma HMW adiponectin /total adiponectin levels was obtained from the values estimated by ELISA. Findings: Our study suggests: i) reduced HMW adiponectin /total adiponectin ratio in diabetic patients (p<0.001) and its association with +10211T/G (rs17846866), +45T/G (rs2241766) and +276G/T (rs1501299) in T2D (p<0.0001), ii) association of the above SNPs with increased Fasting Blood Glucose, Body Mass Index, Triglyceride, Total Cholesterol (p<0.0001). More interestingly, the CGGT haplotype was found to be significantly higher in obese diabetic patients (p=0.007). Interpretation: ADIPOQ +10211T/G (rs17846866), +45T/G (rs2241766) and +276G/T (rs1501299) SNPs along with decreased adiponectin and CGGT haplotype seem to lead towards altered metabolic profile. Interpretation: ADIPOQ +10211T/G (rs17846866), +45T/G (rs2241766) and +276G/T (rs1501299) SNPs along with decreased adiponectin and CGGT haplotype seem to lead towards altered metabolic profile. Funding Statement: Department of Biotechnology, New Delhi, India Declaration of Interests: No conflict of interest exists. Ethics Approval Statement: This study was carried out in agreement with the Declaration of Helsinki as approved by the Institutional Ethical Committee for Human Research (IECHR), Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India (FS/IECHR/2016-9).