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

Joseph Hung⁵  Peter L Thompson⁵  Lyle J Palmer¹  Brendan M McQuillan⁵  Matthew Knuiman⁷  Steven Wiltshire³  Timothy ME Davis⁸  Wendy A Davis⁸  David G Bruce⁸  Nicole M Warrington⁴  Gemma Cadby⁶  John Beilby²  Kirsten E Peters⁸ 

[1]Genetic Epidemiology and Biostatistics Platform, Ontario institute for Cancer Research, Toronto, Canada

[2]School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Western Australia, Australia

[3]Centre for Medical Research, Western Australian Institute for Medical Research, The University of Western Australia, Nedlands, Australia

[4]School of Women’s and Infants’ Health, University of Western Australia, Nedlands, Western Australia, Australia

[5]School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, University of Western Australia, Nedlands, Western Australia, Australia

[6]Centre for Genetic Origins of Health and Disease, University of Western, Nedlands, Western Australia, Australia

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

[8]School of Medicine and Pharmacology, Fremantle Hospital Unit, The University of Western Australia, Nedlands, Western Australia, Australia

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

Others  :  1177740
DOI  :  10.1186/1471-2350-14-15

 received in 2012-10-12, accepted in 2013-01-17,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Peters et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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