Association between the P12A and c1431t polymorphisms in the peroxisome proliferator activated receptor γ (PPARγ) gene and type 2 diabetes

Abstract

Variation in the peroxisome proliferator-activated receptor gamma (PPAR gamma) gene may play a role in the development of type 2 diabetes mellitus. Therefore we investigated the association between the P12A and c1431t polymorphisms in the PPAR gamma gene and type 2 diabetes. The incidence of the P12A polymorphism was determined by PCR-RFLP and the c1431t by single-strand conformation polymorphism analysis in 219 patients with, and 429 without type 2 diabetes. The frequency of the A allele of P12A polymorphism was 0.16 and the t allele of c1431t polymorphism, 0.13 in patients with type 2 diabetes, and 0.13 and 0.12 respectively in subjects without diabetes 3.2% of patients with and 1.4% without type 2 diabetes were A12A. Since the polymorphisms are not linked the association of the 9 possible genotypes with type 2 diabetes was determined. All patients with genotype A12A/c1431c had type 2 diabetes (n = 3, p = 0.038). There was no association between A12A/t1431t and diabetes. DNA sequencing revealed no additional mutations in the coding region of the PPAR gamma gene in genotypes A12A/c1431c or A12A/t1431t. The associations found between polymorphisms in the PPAR gamma gene and type 2 diabetes suggest that either the A12 isofrom is functional leading to a predisposition to type 2 diabetes in homozygotes or that there is a third, unknown mutation linked to the A12/c1431 haplotype which is responsible.

Association of the Pro12Ala Polymorphism in the PPAR-γ2 Gene With 3-Year Incidence of Type 2 Diabetes and Body Weight Change in the Finnish Diabetes Prevention Study

“…In line with our study, the Ala12 allele has been reported to associate with type 2 diabetes in Canadian Oji-Cree women (24). Similarly, Evans et al (25) found an association between the Ala12 allele and type 2 diabetes. Hasstedt et al (26) studied members of familial type 2 diabetic kindreds and reported that the proportion of individuals with type 2 diabetes increased with the number of Ala12 alleles, although the result was not statistically significant.…”

Analysis of the haplotype and linkage disequilibrium of PPARγ gene polymorphisms rs3856806, rs12490265, rs1797912, and rs1175543 among patients with metabolic syndrome in Kazakh of Xinjiang Province

“…In this study, we found that the allele frequency of rs3856806T in the Kazakh control group was 17%. This value is close to the allele frequency of rs3856806T in the Australian population (16.3%; Evans et al, 2001), is higher than that in the South American (13%; Haseeb et al, 2009), Indian (12.3%;Costa et al, 2009), and Italian and French populations (13.3%; Hasstedt et al, 2001), but lower than that among the Han population (21.2%; Liu et al, 2008). Studies examining the relationship between the rs3856806 polymorphism and MS suggest that individuals carrying the T allele show clearly reduced rates of lipid metabolism disorders and high blood pressure, obesity, and diabetes (Chen et al, 2006;Jaziri et al, 2006;Gaulton et al, 2008;Cho et al, 2009;Gallicchio et al, 2009;Bego et al, 2011).…”

Differential effects of the C1431T and Pro12Ala PPARγ gene variants on plasma lipids and diabetes risk in an Asian population

“…Although a meta-analysis evaluating 16 published studies involving more than 3,000 individuals reported a significant increase in diabetes risk (1.25-fold) associated with the most common Pro allele (15), subsequent studies failed to confirm this association (16,17). On the other hand, although it has been postulated that PPAR ␥ may play an im-portant role in lipid metabolism, directly or by inducing the transcription of target genes (18,19), to date, results from studies examining the association between PPAR ␥ 2 variants and lipid profiles are scarcer and also inconsistent (3,13,(20)(21)(22)(23).…”