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

Peters, Kirsten E., Beilby, John, Cadby, Gemma, Warrington, Nicolen M., Bruce, David G., Davis, Wendy A., Davis, Timothy M. E., Wiltshire, Steven, Knuiman, Matthew, McQuillan, Brendan M., Palmer, Lyle J., Thompson, Peter L. and Hung, Joseph (2013) 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. BMC Medical Genetics, 14 1: . doi:10.1186/1471-2350-14-15


Author Peters, Kirsten E.
Beilby, John
Cadby, Gemma
Warrington, Nicolen M.
Bruce, David G.
Davis, Wendy A.
Davis, Timothy M. E.
Wiltshire, Steven
Knuiman, Matthew
McQuillan, Brendan M.
Palmer, Lyle J.
Thompson, Peter L.
Hung, Joseph
Title 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
Journal name BMC Medical Genetics   Check publisher's open access policy
ISSN 1471-2350
Publication date 2013-01-25
Year available 2013
Sub-type Article (original research)
DOI 10.1186/1471-2350-14-15
Open Access Status DOI
Volume 14
Issue 1
Total pages 12
Place of publication London, United Kingdom
Publisher BioMed Central Ltd.
Collection year 2014
Language eng
Subject 2716 Genetics (clinical)
1311 Genetics
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.
Keyword Adiponectin
Insulin resistance and Metabolic syndrome
Type 2 diabetes
Metabolic Syndrome
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
UQ Diamantina Institute Publications
 
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Created: Tue, 10 Jun 2014, 14:54:34 EST by Kylie Hengst on behalf of UQ Diamantina Institute