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Journal of Lipid Research, Vol. 45, 674-685, April 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

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

E. Shyong Tai^*, Dolores Corella^,, Mabel Deurenberg-Yap^**, Xian Adiconis, Suok Kai Chew, Chee Eng Tan^* and Jose M. Ordovas^1,

^* Department of Endocrinology, Singapore General Hospital, Singapore 169608
Genetic and Molecular Epidemiology Unit, Department of Preventive Medicine, University of Valencia, 46010 Valencia, Spain
Nutrition and Genomics Laboratory, Jean Mayer-United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111
^** Research and Information Management Division, Health Promotion Board, Singapore 168937
Epidemiology and Disease Control Division, Ministry of Health, Singapore 169854

¹ To whom correspondence should be addressed. e-mail: jose.ordovas{at}tufts.edu

We investigated the association of C1431T and Pro12Ala polymorphisms at the peroxisome proliferator-activated 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 < 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.

Supplementary key words peroxisome proliferator-activated receptor • polymorphism • insulin • body mass index • fat • diet

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