Frequency and significance of Pro12Ala and Pro115Gln polymorphism in gene for peroxisome proliferation-activated receptor-gamma(2) regarding metabolic parameters in a Caucasian cohort

Peroxisome proliferation-activated receptor-gamma (2), (PPAR gamma (2)) is exclusively expressed in adipose tissue and belongs to the transcriptional regulators of adipocyte differentiation. Recently, two missense single-poin t mutations have been described in the PPAR gamma (2) gene: Pro12Ala and Pr o115Gln. It was our aim to determine the frequency of these polymorphisms i n a Caucasian cohort and to investigate their possible role in the pathogen esis of obesity, type 2 diabetes, and related metabolic disorders. The geno types of 359 subjects (149 males, 210 females) with varying degrees of obes ity and with or without type 2 diabetes were determined. Subsequent to geno mic polymerase chain reaction amplification, the Hpall restriction fragment length polymorphism (RFLP) analysis and the Hindll RFLP analysis were used for genotyping the Pro12Ala and Pro115Gln polymorphism, respectively. For the Pro115Gln polymorphism, all 359 subjects showed wild-type sequence, emp hasizing the very rare occurrence of the mutated allele. For the Pro12Ala p olymorphism, 276 subjects (76.9%) were homozygous for the wild-type allele, 80 (22.3%) were heterozygous, and only 3 (0.8%) were homozygous for the mu tated allele. Genotype frequency was calculated to be 0.88 for the wild-typ e allele and 0.012 for the mutated allele. No significant differences were found in age; gender; body mass index; total cholesterol; low-density, high -density, and very low density lipoproteins; triglycerides; Lp(a); uric aci d; and diabetes manifestation by comparing the different genotypes. Therefo re, a major role of these polymorphisms in the pathogenesis of obesity and diabetes can be excluded.