Objective: To investigate the association of a polymorphism at position 294 ( þ 294T/C) in the Peroxisome Proliferator-activated Receptor d (PPARd) with body mass index (BMI) and the additional role of a gene-to-gene interaction between PPARd, PPARa and PPARg. Design: An association between genetic variations in PPARd, PPARa and PPARg and indices of obesity and metabolism. Subjects: A group of 462 moderately obese (mean BMI 28.977.7) and dyslipidemic, middle-aged (mean age 43.9713.7), Caucasion men and women. Measurements: The three most frequent single-nucleotide-polymorphisms (snp) in PPARd ( þ 294T/C), PPARa (L162V) and PPARg (P12A) were genotyped and associated with clinical parameters. Results: The C allele in PPARd was significantly associated with a lower body mass index. Moreover an interaction between the polymorphisms in PPARa and PPARd on body weight could be demonstrated. Conclusion: Our data provide further evidence for an involvement of PPARd in the regulation of BMI.
Background: The +T294C polymorphism in PPARδ represents a functional SNP affecting transcriptional activity of the PPARδ gene. To address whether this polymorphism is associated with the risk for coronary heart disease and/or plasma lipid levels in women, we studied a group of 967 female patients with hyperlipidaemia in the presence (n=453) or absence (n=514) of coronary heart disease.Methods: 967 female patients with or without coronary heart disease were genotyped using mutagenically separated polymerase chain reaction (MS-PCR). Statistical analysis was performed according to genotype with parameters of lipid metabolism as dependant variables.Results: A highly significant association between the rare C allele and lower plasma HDL concentrations was found in female subjects. The effect remained significant after correcting for multiparametric testing according to Bonferoni and was seen only in subjects with a BMI below the median. Moreover, a significant association of the C-allele with coronary heart disease and BMI was obtained. Regarding the entire group, trends towards higher VLDL and LDL levels were observed.Conclusions: Our data show for the first time that the PPARδ +T294C polymorphism is associated with lipid levels and coronary heart disease in women. However, the molecular mechanism of action remains to be elucidated.
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