Association of EDNRA, but not WNK4 or FKBP1B, polymorphisms with essential hypertension
Association of EDNRA, but not WNK4 or FKBP1B, polymorphisms with essential hypertension
复制标题
DOI：
10.1034/j.1399-0004.2003.00148.x
复制
发表时间：
2003-11-01
影响因子：
3.5
通讯作者：
Morris, BJ
中科院分区：
文献类型：
--
作者：
Benjafield, AV;Katyk, K;Morris, BJ
在一项原发性高血压（HT）遗传基础的研究中，我们检测了三个候选基因的四种变异，这些基因以前没有在HT中研究过。这些基因编码了内皮素受体A型（EDNRA）、蛋白激酶赖氨酸缺陷4 （WNK4）和fk506结合蛋白1B (FKBP1B)，前者可以传导内皮素-1的大部分血管收缩特性，其基因位于17号染色体上的HT连锁区域，后者可以通过增加一氧化氮来降低血压。这些变异是：EDNRA的5'-UTR上的G- > a和第8外显子上的C- >T；对于WNK4，内含子10中的一个四核苷酸重复；对于FKBP1B，外显子4中有一个T- >C。受试者为盎格鲁-凯尔特人白人澳大利亚人，包括155名父母均为HT的HT患者和245名父母均为NT的正常血压（NT）患者。对于EDNRA，我们发现外显子8变异与HT存在弱关联（p = 0.019）， 5'-UTR变异与收缩压和舒张压升高存在关联（p分别= 0.038和0.0031）。WNK4内含子10变异和FKP1B外显子4变异与HT没有关联，但后者与血压有关联（收缩压和舒张压分别为p = 0.015和0.0011）。因此，我们的研究表明EDNRA可能参与必要的HT。
In a study of the genetic basis of essential hypertension (HT), we tested four variants in three candidate genes not previously investigated in HT. These encoded the endothelin receptor type A (EDNRA), which transduces most of the vasoconstrictive properties of endothelin-1, protein kinase lysine deficient 4 (WNK4) whose gene resides in a HT linkage region on chromosome 17, and FK506-binding protein 1B (FKBP1B), which can reduce blood pressure by increasing nitric oxide. The variants were: for EDNRA, a G-->A in the 5'-UTR and C-->T in exon 8; for WNK4, a tetranucleotide repeat in intron 10; and for FKBP1B, a T-->C in exon 4. Subjects were Anglo-Celtic white Australians and included 155 HTs with two HT parents and 245 normotensives (NTs) whose parents were both NT. For EDNRA, we found a weak association of the exon 8 variant with HT (p = 0.019) and association of the 5'-UTR variant with elevation in systolic and diastolic blood pressure (BP) (p = 0.038 and 0.0031, respectively). The WNK4 intron 10 variant and the FKP1B exon 4 variant showed no association with HT, but tracking with BP was seen for the latter (p = 0.015 and 0.0011 for systolic and diastolic BP, respectively). Our study thus suggests possible involvement of EDNRA in essential HT.