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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.

bmc medical genetics

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