Abstract
It was investigated whether pharmacogenetic factors, both as single polymorphism and as gene-gene interactions, have an added value over non-genetic factors in predicting statin response. Five common polymorphisms were selected in apolipoprotein E, angiotensin-converting enzyme, hepatic lipase and toll-like receptor 4. Linear regression models were built and compared on R(2) to estimate the added value of single polymorphisms and gene-gene interactions. The selected polymorphisms and the gene-gene interactions had a small added value in predicting change in low-density lipoprotein cholesterol levels (LDL-c) as response to statins over the non-genetic predictors (P=0.104), and also in predicting LDL-c in non-treated patients (P=0.016). Moreover, four gene-gene interactions with statin therapy were identified. The added value of genetic factors over non-genetic variables is for the greater part produced by gene-gene interactions. This underlines the importance to examine gene-gene interactions in future (pharmaco)genetic research.
