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This Article Full Text Full Text (PDF) All Versions of this Article: EJE-09-0492v1 161/6/845    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Melistas, L. Articles by Yiannakouris, N. PubMed PubMed Citation Articles by Melistas, L. Articles by Yiannakouris, N.

Association of the +45T>G and +276G>T polymorphisms in the adiponectin gene with insulin resistance in nondiabetic Greek women

Departments of¹ , Nutrition and Dietetics² Home Economics and Ecology, Harokopio University of Athens, El. Venizelou 70, 17671 Athens, Greece³ Division of Endocrinology and Metabolism, Department of Internal Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center (BIDMC), Boston, Massachusetts, USA⁴ Nutrition and Genomics Laboratory, Jean Mayer-US Department of Agriculture, Human Nutrition Research Center on Aging (JM-USDA-HNRCA), Tufts University, Boston, Massachusetts, USA

(Correspondence should be addressed to N Yiannakouris; Email: nyiannak{at}hua.gr)

Objective: We explored potential associations of two single nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ; +45T>G, rs2241766 and +276G>T, rs1501299) with circulating total and high-molecular weight (HMW) adiponectin, insulin resistance (IR), and markers of obesity in a healthy Greek female population.

Design and methods: The two SNPs were genotyped in 349 women without diabetes (mean age: 47.0±12.1 years, mean body mass index: 28.9±5.6 kg/m²). Total and HMW adiponectin concentrations, body composition variables, IR parameters, and plasma lipid levels were determined.

Results: In single SNP analysis adjusting for several potential confounders, SNP +276G>T was associated with higher fasting insulin levels (P=0.01) and higher homeostasis model assessment index for IR (HOMA-IR; P=0.009), and SNP +45T>G was associated with lower insulin levels and HOMA-IR (P=0.05 and P=0.07 respectively). No association with total or HMW adiponectin, plasma lipid levels, and body composition variables was observed; however, haplotype analysis revealed that subjects homozygous for the most common +45T/+276G haplotype had lower total adiponectin levels than did noncarriers of this haplotype (P=0.02). The observed differences in HOMA-IR were very significant among women with a higher body fat (BF) percentage ( the population median of 41%; all P0.005), but not among leaner individuals (P for interactions 0.01–0.07), thus suggesting that ADIPOQ effects on insulin sensitivity may depend upon BF status.

Conclusion: Our data suggest a significant role of ADIPOQ variants at positions +45 and +276 in the development of IR in healthy Greek women possibly through an interaction with BF.