title: The PPARgamma Pro12Ala variant is associated with insulin sensitivity in Russian normoglycaemic and type 2 diabetic subjects.
abstract: 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.
authors.affiliation: Department of Molecular Diagnostics, National Research Center, Moscow, Russia. dimitry.chistiakov@lycos.com
authors.forename: Dimitry A
authors.initials: DA
authors.lastname: Chistiakov
authors.forename: Viktor A
authors.initials: VA
authors.lastname: Potapov
authors.forename: Dmitry S
authors.initials: DS
authors.lastname: Khodirev
authors.forename: Minara S
authors.initials: MS
authors.lastname: Shamkhalova
authors.forename: Marina V
authors.initials: MV
authors.lastname: Shestakova
authors.forename: Valery V
authors.initials: VV
authors.lastname: Nosikov
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism*; D012307:Risk Factors; D012426:Russia / Q000453:epidemiology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D047495:PPAR gamma