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

Original Data

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, p_c = 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 (p_c = 0.0375) and serum triglycerides (p_c = 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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