Pharmacogenomics of XXXX : a genome   wide, placebo   controlled cross   over study, using four classes of antihypertensive drugs.

@entity1 @entity101 @entity918 @entity6333 @entity264 @entity71941 @entity9886 @entity71942 @entity58189 @entity3591 @entity71939 @entity2165 @entity71940 @entity734 @entity2179 @entity17610
BACKGROUND: Identification of genetic markers of antihypertensive drug responses could assist in individualization of @entity101 treatment. METHODS AND RESULTS: We conducted a genome-wide association study to identify gene loci influencing the responsiveness of 228 male @entity1 to 4 classes of antihypertensive drugs. The Genetics of Drug Responsiveness in Essential @entity101 (GENRES) study is a double-blind, placebo-controlled cross-over study where each subject received @entity3591 , @entity2179 , @entity918 , and @entity9886 , each as a monotherapy, in a randomized order. Replication analyses were performed in 4 studies with @entity1 of European ancestry (PEAR Study, N=386; GERA I and II Studies, N=196 and N=198; SOPHIA Study, N=372). We identified 3 single-nucleotide polymorphisms within the @entity71939 gene that showed associations with @entity2179 response reaching genome-wide significance (P<5x10(-8))however, this could not be replicated in the PEAR Study using @entity2165 . In addition, 39 single-nucleotide polymorphisms showed P values of 10(-5) to 10(-7). The 20 top-associated single-nucleotide polymorphisms were different for each antihypertensive drug. None of these top single-nucleotide polymorphisms co-localized with the panel of >40 genes identified in genome-wide association studies of @entity101 . Replication analyses of GENRES results provided suggestive evidence for a missense variant ( @entity71940 ) in the @entity6333 ( @entity6333 ) gene influencing @entity9886 response, and for 2 variants influencing @entity918 response, located within or close to the @entity17610 ( @entity71941 ) and @entity58189 ( @entity71942 ) genes. CONCLUSIONS: These data provide some evidence for a link between biology of the glomerular protein @entity6333 and antihypertensive action of angiotensin receptor antagonists and encourage additional studies on @entity264 dehydrogenase   mediated reactions in antihypertensive @entity734 .
