A comprehensive investigation of variants in genes encoding adiponectin ADIPOQ and its receptors ADIPOR1-R2, and their association with serum adiponectin, type 2 diabetes, insulin resistance and the metabolic syndromeReport as inadecuate




A comprehensive investigation of variants in genes encoding adiponectin ADIPOQ and its receptors ADIPOR1-R2, and their association with serum adiponectin, type 2 diabetes, insulin resistance and the metabolic syndrome - Download this document for free, or read online. Document in PDF available to download.

BMC Medical Genetics

, 14:15

Genetic epidemiology and genetic associations

Abstract

BackgroundLow levels of serum adiponectin have been linked to central obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. Variants in ADIPOQ, the gene encoding adiponectin, have been shown to influence serum adiponectin concentration, and along with variants in the adiponectin receptors ADIPOR1 and ADIPOR2 have been implicated in metabolic syndrome and type 2 diabetes. This study aimed to comprehensively investigate the association of common variants in ADIPOQ, ADIPOR1 and ADIPOR2 with serum adiponectin and insulin resistance syndromes in a large cohort of European-Australian individuals.

MethodsSixty-four tagging single nucleotide polymorphisms in ADIPOQ, ADIPOR1 and ADIPOR2 were genotyped in two general population cohorts consisting of 2,355 subjects, and one cohort of 967 subjects with type 2 diabetes. The association of tagSNPs with outcomes were evaluated using linear or logistic modelling. Meta-analysis of the three cohorts was performed by random-effects modelling.

ResultsMeta-analysis revealed nine genotyped tagSNPs in ADIPOQ significantly associated with serum adiponectin across all cohorts after adjustment for age, gender and BMI, including rs10937273, rs12637534, rs1648707, rs16861209, rs822395, rs17366568, rs3774261, rs6444175 and rs17373414. The results of haplotype-based analyses were also consistent. Overall, the variants in the ADIPOQ gene explained <5% of the variance in serum adiponectin concentration. None of the ADIPOR1-R2 tagSNPs were associated with serum adiponectin. There was no association between any of the genetic variants and insulin resistance or metabolic syndrome. A multi-SNP genotypic risk score for ADIPOQ alleles revealed an association with 3 independent SNPs, rs12637534, rs16861209, rs17366568 and type 2 diabetes after adjusting for adiponectin levels OR=0.86, 95% CI=0.75, 0.99, P=0.0134.

ConclusionsGenetic variation in ADIPOQ, but not its receptors, was associated with altered serum adiponectin. However, genetic variation in ADIPOQ and its receptors does not appear to contribute to the risk of insulin resistance or metabolic syndrome but did for type 2 diabetes in a European-Australian population.

KeywordsAdiponectin ADIPOQ ADIPOR Type 2 diabetes Insulin resistance and Metabolic syndrome AbbreviationsMetSMetabolic syndrome

T2DType 2 diabetes

GWASGenome-wide association study

SNPSingle nucleotide polymorphism

tSNPTag single nucleotide polymorphism

BHSBusselton Population Health Survey

CUDASCarotid Ultrasound Disease Assessment Study

FDSFremantle Diabetes Study

IRInsulin resistance

lnHOMA-IRHomeostatic model of assessment

BMIBody mass index

NCEPNational Cholesterol Education Program

HWEHardy-Weinberg equilibrium

LDLinkage disequilibrium.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-14-15 contains supplementary material, which is available to authorized users.

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Author: Kirsten E Peters - John Beilby - Gemma Cadby - Nicole M Warrington - David G Bruce - Wendy A Davis - Timothy ME Davis

Source: https://link.springer.com/







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