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

Abstract

We investigated the association of C1431T and Pro12Ala polymorphisms at the peroxisome proliferatoractivated receptor ␥ (PPAR ␥ ) locus with plasma lipids and insulin resistance-related variables, according to diabetes status, in a large and representative Asian population from Singapore consisting of 2,730 Chinese, 740 Malays, and 568 Indians. Moreover, we estimated the diabetes risk and examined gene-nutrient interactions between these variants and the ratio of polyunsaturated fatty acid to saturated fat (SFA) in determining body mass index (BMI) and fasting insulin. We found differential effects of these gene variants. The Pro12Ala polymorphism was more associated with plasma lipids and fasting glucose concentrations, whereas the C1431T polymorphism was related to the risk of diabetes. Carriers of the 12Ala allele had higher HDL-cholesterol than did Pro12Pro homozygotes ( P Ͻ 0.05), and the effect of the 12Ala allele on fasting glucose was modified by diabetes status ( P Ͻ 0.001). After controlling for confounders, carriers of the T allele had decreased risk of diabetes compared with CC homozygotes [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.58-0.93; P ‫؍‬ 0.011]; this effect was stronger in Indians (OR 0.38, 95% CI 0.15-0.92; P ‫؍‬ 0.032). For both polymorphisms, normal subjects carrying the less prevalent allele had higher BMI ( P Ͻ 0.05). The PUFA/SFA did not modify the effect of these polymorphisms on BMI or insulin.- Tai

Pioglitazone does not enhance the effectiveness of lifestyle modification in preventing conversion of impaired glucose tolerance to diabetes in Asian Indians: results of the Indian Diabetes Prevention Programme-2 (IDPP-2)

“…Genetic differences may also account for their higher susceptibility to insulin resistance and type 2 diabetes mellitus. A few studies in the population have indicated possible differences in the modulating effect of the Pro-Ala polymorphism in the peroxisome proliferator-activated receptor γ compared with white populations [22,23].…”

Retinoid X Receptor Heterodimer Variants and Cardiovascular Risk Factors

“…They reported that the Ala12 allele was protective against diabetes in their study; however, this protective effect, attributable to the Ala12 variant, was absent when the Ala12 variant was presentwith the T allele of c161C T 96) . However, no such opposite interaction or additive effects between c.161C T and p.Pro12Ala was confirmed in another study, and the T allele was associated with a decreased risk of diabetes 97) . Reduced coronary artery disease risk and lower TG were associated with the T allele 98,99) , but a cohort study also indicated an association with higher coronary risk 96) .…”

Pro12Ala polymorphism in PPAR-γ2 and dementia in Chinese nonagenarians/centenarians

“…Therefore, it is reasonable to believe that mortality in the nonagenarian/centenarian Adjusted multiple logistic regression was used to adjust for covariates OR odds ratio, Unadjusted Wald Chi-square test with df=1 was used, Model 1 adjustment made with covariates which might be associated with cognitive function at baseline (P<0.05 shown in Table 1), Model 2 adjustment made with covariates which might be associated with Pro12Ala (P<0.05 shown in Table 2), Model 3 adjustment made with all the covariates group may alter the association between dementia and Pro12Ala Polymorphism in PPAR-γ2. In addition, the prevalence of Ala12 allele varied greatly in different ethnic populations, with the prevalence rate being much lower in Asians than in Caucasians (Chuang et al 2001;Tai et al 2004). Therefore, ethnicity might also be an influencing factor.…”

“…In addition, the prevalence of Ala12 allele varied greatly among different ethnic populations, with the prevalence being much lower in Asians than in Caucasians (Chuang et al 2001;Tai et al 2004). The relationship between Pro12Ala polymorphism in PPAR-γ2 and dementia in the very-elderly population might be different from that in old people aged 60 years and above, and the allele frequency of Ala12 in PPAR-γ2 varies greatly in different ethnic populations.…”