Abstract
We investigated the association of C1431T and Pro12Ala polymorphisms at the peroxisome proliferator-activated receptor gamma (PPARgamma) 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 < 0.05), and the effect of the 12Ala allele on fasting glucose was modified by diabetes status (P < 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 < 0.05). The PUFA/SFA did not modify the effect of these polymorphisms on BMI or insulin.
Highlights
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
Our aims were as follows: 1) to study the association of common variants at the PPAR␥ locus (C1431T and Pro12Ala polymorphisms) with plasma lipids and insulin resistance-related variables, depending on the degree of glucose tolerance, in a large and representative Asian population from Singapore; 2) as the Singapore population comprises three ethnic groups (Chinese, Malays, and Indians) that exhibit significantly different incidences of diabetes, our second aim was to estimate the risk of diabetes associated with these polymorphisms; and 3) considering that a gene-nutrient interaction between the Pro12Ala variant and the ratio of polyunsaturated fatty acid to saturated fat (SFA) in determining body mass index (BMI) and fasting insulin has been described in Caucasians [28], our third objective was to examine this interaction in the Singaporean population
The Ala12 allele of the Pro12Ala polymorphism was associated with a significantly lower risk of impaired glucose tolerance (IGT), but it was not associated with diabetes risk in Singaporeans
Summary
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. Our aims were as follows: 1) to study the association of common variants at the PPAR␥ locus (C1431T and Pro12Ala polymorphisms) with plasma lipids and insulin resistance-related variables, depending on the degree of glucose tolerance, in a large and representative Asian population from Singapore; 2) as the Singapore population comprises three ethnic groups (Chinese, Malays, and Indians) that exhibit significantly different incidences of diabetes, our second aim was to estimate the risk of diabetes associated with these polymorphisms; and 3) considering that a gene-nutrient interaction between the Pro12Ala variant and the ratio of polyunsaturated fatty acid to saturated fat (SFA) in determining body mass index (BMI) and fasting insulin has been described in Caucasians [28], our third objective was to examine this interaction in the Singaporean population
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