Haplotypes of genetic variants of PPARGC1 and cardiovascular disease

Obesity is a worldwide problem and as a consequence the incidence of associated disorders like type 2 diabetes, coronary heart disease and hypertension increases. Environmental (e.g. nutrition) and endogenous (e.g. genetic) factors affect the development of these disorders. PPARGC1 (peroxisome proliferator-activator receptor-gamma, coactivator1) has been described as a major factor regulating lipid and glucose metabolism. Variants in PPARGC1 have been associated with obesity and related disorders. We now investigated three known polymorphisms (Gly482Ser, Thr528Thr and Met612Thr), which are located in exon 10 and 11 of PPARGC1 and their association to cardivascular disease. We determined the relationship to disease risk in a nested case-control study of the prospective EPIC (European prospective investigation into cancer and nutrition)-Potsdam cohort (nested-case-control-study, total=27.548, nested=1259; controls=842, cases=404) and in a cross-sectional design the relation to Intima-Media-Thickness, a surrogate parameter of CVD, within the MeSyBePo (Metabolic Syndrome Berlin Potsdam)-study (n=1.188, controls=538, cases=448). Genotyping was performed by TaqMan-5'-nuclease assay (7900HT, ABI). After haplotype calculation, the most common (more than 10% appearance) have been used for statistical analyses.

Even in the crude analysis (adjustement for age and sex only), no association between any SNP or any of the investigated endpoints was found. Neither for the combined endpoint nor for myocardial infarction or stroke a significant association was observed. Comparably we found no association with IMT in the MesyBePo-cohort.

Our data suggest, that the here investigated genetic variants within PPARGC-1 are not linked to cardiovascular disease.