Identification and functional analysis of CORIN variants in hypertensive patients.
Identification and functional analysis of CORIN variants in hypertensive patients.
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高血压患者CORIN变异的鉴定和功能分析
DOI：
10.1002/humu.23318
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发表时间：
2017-12
期刊：
影响因子：
3.9
通讯作者：
Wu Q
中科院分区：
文献类型：
--
作者：
Zhang Y;Zhou T;Niu Y;He M;Wang C;Liu M;Yang J;Zhang Y;Zhou J;Fukuda K;Qin J;Dong N;Wu Q
Corin是一种激活心钠素(ANP)的丝氨酸蛋白酶。已有报道称高血压患者中存在Corin基因变异。然而，到目前为止，Corin变异体在高血压患者中的流行率仍不清楚。为了了解Corin变异体在高血压中的患病率和功能意义，我们对300名正常人群和401名中国人的Corin外显子进行了测序，确定了9个非同义变异体，其中8个是以前没有特征的。其中，突变c.131a>；G(p.Tyr13Cys)、c.376G>；T(p.Asp95Tyr)、c.1094T>；G(p.Leu334Trp)和c.1667G>；A(p.Arg525His)在正常人和高血压患者中发生的情况相似。在高血压患者中，c1139G>；A(p.Arg349His)、c.2689C>；T(p.Pro866Ser)和c.2864C>；T(p.Thr924Met)各发现一次。变异c.1683G>；T(p.Arg530Ser)多见于高血压患者[10/401(2.5%)vs 1/300(0.3%)；P=0.023]，并在另一独立队列中得到证实[高血压患者9/368(2.44%)，正常人群2/377(0.53%)；P=0.033]。在生化和基于细胞的功能研究中，突变体p.Arg530Ser和p.Thr924Met，而不是p.Tyr13Cys，p.Asp95Tyr，p.Leu334Trp，p.Arg349His，p.Arg525His和p.Pro866Ser，显示出前ANP加工活性降低，这分别是由于内质网滞留和酶原激活不良所致。这些结果表明，损害Corin功能的遗传变异在普通人群中并不少见，这种变异可能是高血压的一个重要因素。
Corin is a serine protease that activates atrial natriuretic peptide (ANP). CORIN gene variants have been reported in patients with hypertension. To date, however, the prevalence of CORIN variants in hypertensive patients remains unknown. To understand the prevalence and functional significance of CORIN variants in hypertension, we sequenced CORIN exons in 300 normal and 401 hypertensive individuals in a Chinese population and identified nine nonsynonymous variants, of which eight were not characterized previously. Among them, variants c.131A > G (p.Tyr13Cys), c.376G > T (p.Asp95Tyr), c.1094T > G (p.Leu334Trp), and c.1667G > A (p.Arg525His) occurred similarly in both normal and hypertensive individuals. Variants c1139G > A (p.Arg349His), c.2689C > T (p.Pro866Ser), and c.2864C > T (p.Thr924Met) were found once each in hypertensive individuals. Variant c.1683G > T (p.Arg530Ser) occurred preferentially in hypertensive individuals [10/401 (2.5%) vs. 1/300 (0.3%) in normal individuals; P = 0.023], which was confirmed in another independent cohort [9/368 (2.44%) in hypertensive and 2/377 (0.53%) in normal individuals; P = 0.033]. In biochemical and cell-based functional studies, variants p.Arg530Ser and p.Thr924Met, but not p.Tyr13Cys, p.Asp95Tyr, p.Leu334Trp, p.Arg349His, p.Arg525His, and p.Pro866Ser, exhibited reduced pro-ANP processing activity, which was caused by endoplasmic reticulum retention and poor zymogen activation, respectively. These results indicate that genetic variants impairing corin function are not uncommon in general populations and that such variants may be an important contributing factor in hypertension.
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影响因子：
3.7
作者：
Hu W;Chen S;Song Y;Zhu F;Shi J;Han X;Zhou D;Zhi Z;Zhang F;Shen Y;Ma J;Liu CF;Peng H
通讯作者：
Peng H
DOI：
10.1152/ajpheart.00399.2010
发表时间：
2010-11-01
影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Schwede, T
DOI：
10.1161/circheartfailure.109.903849
发表时间：
2010-03
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Dong N;Chen S;Yang J;He L;Liu P;Zheng D;Li L;Zhou Y;Ruan C;Plow E;Wu Q
通讯作者：
Wu Q