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Rev Diabet Stud, 2008, 5(1):28-37 DOI 10.1900/RDS.2008.5.28

Adiponectin and Adiponectin Receptor Gene Variants in Relation to Type 2 Diabetes and Insulin Resistance-Related Phenotypes

Viktor A. Potapov1, Dimitry A. Chistiakov1, Anna Dubinina2, Minara S. Shamkhalova2, Marina V. Shestakova2, Valery V. Nosikov1

1National Research Center GosNIIgenetika, 117545 Moscow, Russia
2Endocrinological Research Center, 117036 Moscow, Russia
Address correspondence to: Dimitry A. Chistiakov, e-mail: dimitry.chistiakov@eudoramail.com

Manuscript submitted April 15, 2008; resubmitted May 22, 2008; accepted May 25, 2008.

Keywords: type 2 diabetes, adiponectin, insulin resistance, haplotype, ADIPOQ, ADIPOR1, ADIPOR2

Abstract

BACKGROUND: Alterations in adiponectin-mediated pathways are known to be associated with glucose intolerance, insulin resistance (IR), obesity, and type 2 diabetes (T2D) mellitus. Genetic variations in adiponectin (ADIPOQ) and adiponectin 1 and 2 receptor (ADIPOR1 and ADIPOR2) could have effects on IR-related phenotypes and T2D. Here we examine whether the polymorphic markers rs2241766 (ADIPOQ), rs22753738 (ADIPOR1), rs11061971 and rs16928751 (both in ADIPOR2) are implicated in susceptibility to T2D in a Russian population. METHODS: The polymorphic markers were genotyped in 129 T2D patients, and 117 non-diabetic controls, by polymerase chain reaction (PCR) restriction fragment length polymorphism approach. In the subjects, biochemical characteristics including serum insulin, plasma glucose and serum lipids/lipoproteins were measured and compared for correlation with the genetic variations studied. RESULTS: Allele T of rs11061971 and allele A of rs16928751 showed association with higher risk of diabetes providing odds ratios (OR) of 2.05 (p = 0.0025) and 1.88 (p = 0.018), respectively. Haplotype A-G consisting of allele A of rs11061971 and allele G of rs16928751 was associated with reduced risk of T2D (OR = 0.59, pc = 0.0224). Compared to other variants, diabetic patients double homozygous for A/A of rs16928751 and G/G of rs16928751 had decreased homeostasis model assessment-insulin resistance (pc = 0.0375) and serum triglycerides (pc = 0.0285). CONCLUSIONS: The variants of ADIPOR2 confer susceptibility to T2D and are associated with some IR-related phenotypes in the Russian study population.

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