RESUMO
The second isoform of the PPARgamma2 is specific for adipose tissue. In adipocytes, this isoform is involved in the regulation of adipogenesis and lipid storage, insulin and glucose metabolism. Pro12Ala, a missense mutation in exon 2 of PPARG, reduces transcriptional activity of PPARgamma2 and is shown to be associated with increased insulin sensitivity and protection from T2D. Previously, this polymorphism has never been assessed in a Russian population for its relationship to T2D, insulin resistance, and diabetes-related metabolic traits. In this study, we tested 588 Russian T2D patients and 597 normoglycaemic controls. Carriers of the Pro12 allele and subjects homozygous for Pro/Pro had significantly increased risk of developing T2D (OR 1.43 and 2.04, respectively). In Pro/Pro homozygotes, adjustment for potential confounding risk factors resulted in reducing the OR value from 2.04 to 1.69, but the association remained significant (p=0.046).The Pro/Pro genotype also showed association with increased levels of fasting insulin (p=0.019) in non-diabetic controls and elevated serum triglycerides (p=0.019) in T2D patients. Compared with other genotypes, non-diabetic and diabetic subjects homozygous for Pro/Pro had a significantly higher HOMA-IR score and reduced ISI value. This observation strongly supports the implication of the PPARG Pro12Ala in insulin resistance and T2D in a Russian population.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2 , Resistência à Insulina/genética , PPAR gama/genética , PPAR gama/metabolismo , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Predisposição Genética para Doença/epidemiologia , Variação Genética , Genótipo , Homozigoto , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Federação Russa/epidemiologiaRESUMO
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.
