Effects of two common polymorphisms of peroxisome proliferator-activated receptor-gamma gene on metabolic syndrome.
BACKGROUND
Peroxisome proliferator-activated receptor (PPAR)gamma is involved mainly in adipocyte differentiation and has been suggested to play an important role in the pathogenesis of insulin resistance and atherosclerosis. We investigated the frequencies of two common polymorphisms of PPARgamma gene, exon 6 C-->T substitution and exon B Pro12Ala in healthy subjects and analyzed the correlations between the different genotypes and insulin resistance, metabolic syndrome and cardiovascular risk factors.


METHODS
Anthropometric measurements, fasting glucose, insulin and lipid profiles were measured in 253 Korean females. Homeostatic model assessments and quantitative insulin sensitivity check indices were calculated. Metabolic syndrome was diagnosed according to the NCEP-ATP III guidelines and the Western Pacific Region of WHO for obesity criteria for waist circumference. Polymerase chain reaction (PCR)-restriction fragment-length polymorphism and real-time PCR were performed for genotyping of the DNAs.


RESULTS
For C161T polymorphism, allele frequencies were 0.804 and 0.196 for T allele, and 0.947 for proline and 0.053 for alanine. There was no Ala12Ala homozygote in the population. No differences were seen in the mean values of age, body mass index (BMI), blood pressure, fasting blood glucose level, fasting insulin levels, HOMA and QUICKI among different genotypes when analyzed as a whole, except that subjects with Pro12Ala had significantly higher body weight than those with Pro12Pro genotype. However, mean BMI, percent body fat and weight showed significant differences between genotypes in younger age group (< or =50 years). Although overall prevalence of metabolic syndrome had no association with the genotypes, the prevalence of decreased high-density lipoprotein cholesterol component was lower in those with the T allele than in those with the CC genotype. There was no association of the genotypes with glucose tolerance status. When the subjects were divided into four groups according to the combination of the genetic alleles of the two polymorphisms, subjects having Pro12Ala and T allele, simultaneously, showed significantly higher mean weight than those without Ala allele. Pro12Ala polymorphism seems to affect body weight, similar to the previous studies, and the effect was potentiated with the presence of T allele of C161T polymorphism.


CONCLUSIONS
Although either polymorphism failed to show significant association with insulin resistance, the fact that the prevalence of decreased HDL-C was lower in those with the T allele of C161T polymorphism suggests that this polymorphism might have a protective effect on atherosclerotic lipid profiles, which needs further investigation.
Rhee
Eun Jung
EJ
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Oh
Ki Won
KW
Lee
Won Young
WY
Kim
Se Yeon
SY
Oh
Eun Sook
ES
Baek
Ki Hyun
KH
Kang
Moo Il
MI
Kim
Sun Woo
SW
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D005260:Female; D006801:Humans; D024821:Metabolic Syndrome / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D011237:Predictive Value of Tests
D047495:PPAR gamma