A corin variant identified in hypertensive patients that alters cytoplasmic tail and reduces cell surface expression and activity.
A corin variant identified in hypertensive patients that alters cytoplasmic tail and reduces cell surface expression and activity.
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在高血压患者中发现的 Corin 变体可改变细胞质尾部并降低细胞表面表达和活性
DOI：
10.1038/srep07378
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发表时间：
2014-12-09
影响因子：
4.6
通讯作者：
Wu Q
中科院分区：
文献类型：
--
作者：
Zhang Y;Li H;Zhou J;Wang A;Yang J;Wang C;Liu M;Zhou T;Zhu L;Zhang Y;Dong N;Wu Q
Corin是一种膜结合蛋白酶，通过激活利钠肽调节血压，其变异体与非裔美国人的高血压和心脏病有关。在这项研究中，我们进行了有针对性的外显子组测序，并确定了插入变异，c.102_103insA，在外显子1的CORIN基因。对两个独立队列的分析显示，该变异优先出现在高血压患者中（38/795或4.78% vs.4/632或0.63%，正常个体，p= 4.14E-6）。插入移动了阅读框架，导致corin变体具有截短的胞质尾。在基于细胞的研究中，corin变体在高尔基体中表现出较差的运输，降低的细胞表面表达和酶原活化以及低的利钠肽加工活性。与携带野生型等位基因的正常个体相比，携带变异等位基因的个体血浆corin水平较低[0.59 ± 0.07 ng/mL（n = 25）vs. 0.91 ± 0.02 ng/mL（n = 215），p<0.001]，血浆N末端前心钠素（NT-pro-ANP）水平较高[2.39 ± 3.6 nmol/L（n = 21）vs. 0.87 ± 0.6 nmol/L（n = 48），p= 0.005]。 这些结果表明，变异改变corin的结构和损害利钠肽加工活性在体内。结果强调corin缺陷是高血压的重要潜在机制。
Corin is a membrane-bound protease that regulates blood pressure by activating the natriuretic peptides.CORINvariants have been associated with hypertension and heart disease in African Americans. In this study, we conducted targeted exome sequencing and identified an insertion variant, c.102_103insA, in exon 1 of theCORINgene. Analysis of two independent cohorts showed that the variant was preferentially present in hypertensive patients (38/795 or 4.78%vs. 4/632 or 0.63% in normal individuals,p= 4.14E-6). The insertion shifted the reading frame, resulting in a corin variant with a truncated cytoplasmic tail. In cell-based studies, the corin variant exhibited poor trafficking in the Golgi, reduced cell surface expression and zymogen activation and low natriuretic peptide processing activity. Compared with normal individuals with the wild-type allele, individuals with the variant allele had lower levels of plasma corin [0.59 ± 0.07 ng/mL (n = 25)vs. 0.91 ± 0.02 ng/mL (n = 215),p<0.001] and higher levels of plasma N-terminal pro-atrial natriuretic peptide (NT-pro-ANP) [2.39 ± 3.6 nmol/L (n = 21)vs. 0.87 ± 0.6 nmol/L (n = 48),p= 0.005]. These results indicate that the variant altered corin structure and impaired the natriuretic peptide processing activityin vivo. The results highlight corin defects as an important underlying mechanism in hypertension.
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DOI：
10.1016/j.cca.2011.10.032
发表时间：
2012-02-18
期刊：
Clinica chimica acta; international journal of clinical chemistry
影响因子：
--
作者：
Dong N;Chen S;Wang W;Zhou Y;Wu Q
通讯作者：
Wu Q
DOI：
10.1161/hypertensionaha.113.01344
发表时间：
2013-11
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Cannone V;Huntley BK;Olson TM;Heublein DM;Scott CG;Bailey KR;Redfield MM;Rodeheffer RJ;Burnett JC Jr
通讯作者：
Burnett JC Jr
影响因子：
20.1
作者：
Nakayama, T;Soma, M;Furuya, K
通讯作者：
Furuya, K
DOI：
10.1073/pnas.0407234102
发表时间：
2005-01-18
影响因子：
11.1
作者：
Chan, JCY;Knudson, O;Wu, QY
通讯作者：
Wu, QY
影响因子：
3.7
作者：
Larsen BR;Steffensen SD;Nielsen NV;Friis S;Godiksen S;Bornholdt J;Soendergaard C;Nonboe AW;Andersen MN;Poulsen SS;Szabo R;Bugge TH;Lin CY;Skovbjerg H;Jensen JK;Vogel LK
通讯作者：
Vogel LK