Rimpelä Jenni M, Kontula Kimmo K, Fyhrquist Frej, Donner Kati M, Tuiskula Annukka M, Sarin Antti-Pekka, Mohney Robert P, Stirdivant Steven M, Hiltunen Timo P
Department of Medicine, University of Helsinki, Finland.
Helsinki University Hospital, Helsinki, Finland.
Pharmacogenomics. 2017 Apr;18(5):445-458. doi: 10.2217/pgs-2016-0204. Epub 2017 Mar 29.
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).
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.
We provide support for two pharmacogenomic markers for beta-blockers and angiotensin receptor antagonists.
利用LIFE研究中的芬兰患者，在GENRES中复制比索洛尔和氯沙坦降压作用的全基因组关联。
我们分析了927名芬兰LIFE患者（467名使用阿替洛尔，460名使用氯沙坦）中4个单核苷酸多态性（SNP）与阿替洛尔的关联以及3个SNP与氯沙坦反应的关联。
rs2514036，ACY3转录起始位点的一个变异，与LIFE研究中男性对阿替洛尔的血压反应相关。在GENRES研究中，对比索洛尔的反应与N - 乙酰苯丙氨酸和苯丙氨酸（分别为ACY3底物和终产物）的基线血浆水平相关。NPHS1变异rs3814995与LIFE研究中氯沙坦的效果相关。
我们为β受体阻滞剂和血管紧张素受体拮抗剂的两个药物基因组学标记提供了支持。
