Abstract
Adiponectin is a prime determinant of the status of insulin resistance. Association studies between adiponectin (ADIPOQ) gene single nucleotide polymorphisms (SNPs) and metabolic diseases have been reported earlier. However, results are ambiguous due to apparent contradictions. Hence, we investigated (1) the association between ADIPOQ SNPs: −11377C/G, +10211T/G, +45T/G and +276G/T for the risk towards type 2 diabetes (T2D) and, (2) genotype-phenotype association of these SNPs with various biochemical parameters in two cohorts. Genomic DNA of diabetic patients and controls from Gujarat and, Jammu and Kashmir (J&K) were genotyped using PCR-RFLP, TaqMan assay and MassArray. Transcript levels of ADIPOQ were assessed in visceral adipose tissue samples, and plasma adiponectin levels were estimated by qPCR and ELISA respectively. Results suggest: (i) reduced HMW adiponectin/total adiponectin ratio in Gujarat patients and its association with +10211T/G and +276G/T, and reduced ADIPOQ transcript levels in T2D, (ii) association of the above SNPs with increased FBG, BMI, TG, TC in Gujarat patients and (iii) increased GGTG haplotype in obese patients of Gujarat population and, (iv) association of −11377C/G with T2D in J&K population. Reduced HMW adiponectin, in the backdrop of obesity and ADIPOQ genetic variants might alter metabolic profile posing risk towards T2D.
Highlights
Adiponectin is a prime determinant of the status of insulin resistance
Obesity related factors like Body Mass Index (BMI), total cholesterol (TC), TG and Low-density lipoprotein cholesterol (LDL-c) were significantly elevated (p < 0.0001, p = 0.0360 and p = 0.001, respectively) while high-density lipoprotein cholesterol (HDL-c) was significantly decreased (p < 0.0001) in patients as compared to controls in Gujarat population while in the Jammu and Kashmir (J&K) population BMI (p = 0.015), Fasting Blood Glucose (FBG) (p < 0.0001) and TG (p = 0.001) levels were significantly higher in type 2 diabetes (T2D) patients
The findings in Gujarat population are further linked with reduced levels of high molecular weight (HMW) adiponectin and disease-associated risk factors like FBG, BMI and lipid parameters thereby suggesting their crucial role in metabolic disease susceptibility
Summary
Association studies between adiponectin (ADIPOQ) gene single nucleotide polymorphisms (SNPs) and metabolic diseases have been reported earlier. Results suggest: (i) reduced HMW adiponectin/ total adiponectin ratio in Gujarat patients and its association with +10211T/G and +276G/T, and reduced ADIPOQ transcript levels in T2D, (ii) association of the above SNPs with increased FBG, BMI, TG, TC in Gujarat patients and (iii) increased GGTG haplotype in obese patients of Gujarat population and, (iv) association of −11377C/G with T2D in J&K population. The fine-tuned balance between the pro- and anti-inflammatory adipokines gets altered leading to various metabolic disorders[2]. These bioactive peptides act locally and distally to calibrate and fine tune various metabolic pathways. We aimed to study the genotype-phenotype association of the above-mentioned SNPs with Fasting Blood Glucose (FBG), Body Mass Index (BMI), plasma lipid profile and T2D
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