The effects of C161->T polymorphisms in exon 6 of peroxisome proliferator-activated receptor-gamma gene on insulin resistance and the prevalence of metabolic syndrome in healthy korean subjects

Rhee, Eun Jung; Lee, Won Young; Kim, Se Yeon; Oh, Eun Sook; Baek, Ki Hyun; Oh, Ki Won; Park, Kyung Chang; Kang, Moo Il; Kim, Sun Woo

Abstract

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR)gamma is a member of nuclear receptor family, known to be involved mainly in adipocyte differentiation and suggested to play an important role in the pathogenesis of insulin resistance and diabetes. Although PPAR gamma Pro12Ala polymorphism has been massively studies under the hypothesis that it could have a protective effect against the development of diabetes, studies on the association of other PPAR gamma polymorphisms with insulin resistance and diabetes are scarce. We investigated the frequencies of PPAR gamma exon 6 C->T substitution in healthy Koreans and the correlations between different genotypes and insulin resistance and the prevalence of metabolic syndrome.
METHODS
In total 335 Korean adults (37-73 years, mean age 52 +/- 7 years, 72 males, 263 females), body mass indices (BMI, Kg/m2) were calculated from height and weight measurements and blood pressure, fasting blood glucose, fasting insulin, serum lipid profiles were measured. Homeostatic model assessment (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated as insulin resistance indices. Metabolic syndrome was diagnosed according to Adult Treatment Panel (ATP) III guidelines, substituting waist circumference with BMI. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was done in all blood samples and statistical analysis were performed among different genotypes CC, CT and TT.
RESULTS
The frequency of CC genotype was 64.5%, 31.6% for CT and 3.9% for TT genotype and the frequency of C allele was 0.803 and 0.197 for T allele, which was in Hardy-Weinberg equilibrium (p>0.05). There were no differences in the mean values of age, percent body fat (%), blood pressure, fasting blood glucose level, fasting insulin levels and HOMA, QUICKI and lipid battery among different genotypes (p>0.05). The prevalences of metabolic syndrome were not different among different genotypes, however, when prevalences of each components of metabolic syndrome was compared individually, the prevalence of fasting hyperglycemia (>or=110 mg/dL) was higher in group with T allele than group with CC genotype (p<0.05). In contrast, the prevalence of low high-density lipoprotein cholesterol (HDL-C)(<40 mg/dL in men, <50 mg/dL in women) was lower in group with T allele than group with CC genotype (p<0.05). The prevalences of other components did not show any differences among different genotypes. When subjects were divided in 3 groups by fasting blood glucose, that is, normal, fasting hyperglycemia and diabetes, there were no differences in prevalences among the genotypes.
CONCLUSION
The frequency of PPAR gamma exon 6 C->T polymorphism in Korean people was similar to that in caucasians. Although insulin resistance indices, BMI, prevalence of metabolic syndrome were not different among different genotypes, the fact that the prevalence of fasting hyperglycemia was higher and that of low HDL-C was lower in group with T allele suggests the role of this polymorphism in negative way in glucose metabolism and in positive way in atherosclerosis, which needs further investigation.