We were able to confirm only one association, that of the common Pro12Ala polymorphism in peroxisome proliferator-activated receptor-gamma(PPARgamma) with type 2 diabetes.
In view of inter-individual variability in therapeutic response to pioglitazone, this study was designed to search for an association between type 2 diabetes mellitus and Pro12Ala single-nucleotide polymorphism (SNP) in PPARγ (SNP rs1801282) and to investigate whether these genetic variants affect pioglitazone response in an Iranian population.
Together, these results showed that PPARGPro12Ala and PPARGC1A Gly482Ser variants are associated, alone and in interaction, with insulin and glucose homeostasis and suggest that gene-gene interactions should be taken into account in candidate gene studies of T2DM to identify subjects with markedly different risks of developing the disease.
Three-site haplotype analysis in the PPARG locus using the 2 marginally associated SNPs (P/rs11715073 and P/rs3892175) in combination with Pro12 Ala (P/rs1801282) revealed a strong association of 1 "risk" (CGC) (P = .003, permutation P = .015) and 1 "protective" (CAC) (P = .001, permutation P = .005) haplotype associated with T2D.
The pharmacological activators of PPARγ include thiazolidinediones (TZDs), which are insulin sensitizers used in the treatment of type 2 diabetes mellitus (T2DM), despite some drawbacks.
Pro12Ala polymorphism of the PPARG2 gene is associated with type 2 diabetes mellitus and peripheral insulin sensitivity in a population with a high intake of oleic acid.
The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR-gamma) gene is inversely associated with body mass index (BMI), changes in BMI and the risk to develop type 2 diabetes mellitus.
Although our data indicate that the PPARG2 gene variants, independently, have no association with type 2 diabetes mellitus, the 2-loci genotype analysis involving -1279G/A and Pro12Ala variants and the 3-loci haplotype analysis have shown a significant association with type 2 diabetes mellitus in this South Indian population.
The combination of large-scale DNA sequencing and functional testing in the laboratory reveals that approximately 1 in 1,000 individuals carries a variant in PPARG that reduces function in a human adipocyte differentiation assay and is associated with a substantial risk of T2D.
Rosiglitazone (RG) is a well-known activator of peroxisome proliferator-activated receptor-gamma (PPAR<i>γ</i>) and used to treat hyperglycemia and type 2 diabetes; however, its clinical application has been confounded by adverse side effects.
The present study demonstrates that the AA genotype of the Gly482Ser polymorphism in the PPARGC1 gene might be a risk factor for diabetic retinopathy in the Slovene population (Caucasians) with type 2 diabetes (odds ratio 2.7, 95% confidence interval 1.0-6.8), whereas the Pro12Ala polymorphism of the PPARgamma gene failed to confer susceptibility to diabetic retinopathy.
Nominal interactions were observed for sleep duration and PPARGrs1801282, CRY2 rs7943320 and HNF1B rs4430796 in influencing risk of type 2 diabetes (p < 0.05).
Although the study was carried out on a sufficiently large sample, the conclusions do not support a major role for the Pro12Ala substitution of the PPAR-gamma gene in the etiology of type 2 diabetes.
Rare monogenic mutations in PPARgamma have a limited impact on the health of the population due to their low frequency but are associated with severe phenotypes such as severe insulin resistance, partial lipodystrophy, type 2 diabetes and hypertension.
The objective of the study was to determine the association of the IRS1 (rs1801278), CAPN10 (rs3792267), TCF7L2 (rs7903146 and rs12255372), and PPARG (rs1801282) gene polymorphisms with T2D, in two different Mexican populations.
In conclusion, our findings support the hypothesis that ENPP1-121Q is involved in the genetic susceptibility of T2D in the Tunisian population, while the PPARgamma-12Ala allele may confer protection against overweight.
Four of the nine SNPs revealed a significant association with T2D; PPARG2 (Pro12Ala) [odds ratio (OR) 0.12; 95% confidence interval (CI) (0.03-0.52); p = 0.005], IGF2BP2 [OR 1.37; 95% CI (1.04-1.82); p = 0.027], TCF7L2 [OR 1.64; 95% CI (1.20-2.24); p = 0.001] and FTO [OR 1.46; 95% CI (1.11-1.93); p = 0.007] after adjusting for age, sex and BMI.
These results indicate that the PPARgamma C161-->T polymorphism may reduce the risk of severe atherogenesis by modulation of adipose metabolism, especially triglycerides and apoB, in Chinese patients with CAD and T2DM.
Genetic variants in CDKN2A/B, CDKAL1, TCF7L2, TCF2, MC4R, and PPARG showed a nominal association with type 2 diabetes (P<or=0.05), of whom the three first would stand correction for multiple testing: CDKN2A/B rs10811661, OR: 1.26 (1.12-1.43) P = 1.8*10(-4); CDKAL1 rs10946398, OR: 1.23 (1.09-1.39); P = 7.1*10(-4), and TCF7L2 rs7903146, OR: 1.61 (1.19-2.18) P = 2.3 * 10(-3).
The Pro12Ala Single Nucleotide Polymorphism (SNP) of the Peroxisome Proliferator-Activated Receptor gamma 2 (PPAR-gamma 2) has been associated with insulin resistance and type 2 diabetes (T2D) and also inconsistently with obesity.
Peroxisome proliferator-activated receptor-gamma coactivator-1alpha polymorphism is not associated with essential hypertension and type 2 diabetes mellitus in Chinese population.