Replicated evidence for aminoacylase 3 and nephrin gene variations to predict antihypertensive drug responses

Aim: To replicate the genome-wide associations of the antihypertensive effects of bisoprolol and losartan in GENRES, using the Finnish patients of LIFE study. Patients & methods: We analyzed association of four SNPs with atenolol and three SNPs with losartan response in 927 Finnish LIFE patients (467 for atenolol and 460 for losartan). Results: rs2514036, a variation at a transcription start site of ACY3, was associated with blood pressure response to atenolol in men in LIFE. Response to bisoprolol was correlated to baseline plasma levels of N-acetylphenylalanine and phenylalanine (ACY3 substrate and end product, respectively) in GENRES study. NPHS1 variation rs3814995 was associated with losartan effect in LIFE. Conclusion: We provide support for two pharmacogenomic markers for beta-blockers and angiotensin receptor antagonists.