Association of the T+294C polymorphism in PPAR δ with low HDL cholesterol and coronary heart disease risk in women

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.