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Open Access Highly Accessed Research article

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

Kirsten E Peters1, John Beilby23, Gemma Cadby4, Nicole M Warrington5, David G Bruce1, Wendy A Davis1, Timothy ME Davis1, Steven Wiltshire6, Matthew Knuiman7, Brendan M McQuillan8, Lyle J Palmer9, Peter L Thompson8 and Joseph Hung8*

Author Affiliations

1 School of Medicine and Pharmacology, Fremantle Hospital Unit, The University of Western Australia, Nedlands, Western Australia, Australia

2 Department of Diagnostic Molecular Genomics, PathWest, Queen Elizabeth II Medical Centre, Nedlands, Nedlands, Western Australia, Australia

3 School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Western Australia, Australia

4 Centre for Genetic Origins of Health and Disease, University of Western, Nedlands, Western Australia, Australia

5 School of Women’s and Infants’ Health, University of Western Australia, Nedlands, Western Australia, Australia

6 Centre for Medical Research, Western Australian Institute for Medical Research, The University of Western Australia, Nedlands, Australia

7 School of Population Health, The University of Western Australia, Nedlands, Western Australia, Australia

8 School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, University of Western Australia, Nedlands, Western Australia, Australia

9 Genetic Epidemiology and Biostatistics Platform, Ontario institute for Cancer Research, Toronto, Canada

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BMC Medical Genetics 2013, 14:15  doi:10.1186/1471-2350-14-15

Published: 25 January 2013

Abstract

Background

Low 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.

Methods

Sixty-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.

Results

Meta-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).

Conclusions

Genetic 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.

Keywords:
Adiponectin; ADIPOQ; ADIPOR; Type 2 diabetes; Insulin resistance and Metabolic syndrome