Hum Mutat. 2017 Aug 31. doi: 10.1002/humu.23318. [Epub ahead of print]
题目：
Identification and functional analysis of CORIN variants in hypertensive patients.
作者：
Zhang Y1, Zhou T1, Niu Y1, He M1, Wang C1, Liu M1, Yang J2, Zhang Y3, Zhou J4, Fukuda K5, Qin J5, Dong N1,2,3, Wu Q1,3,5.
单位：
1The Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People's Republic of China.
2Department of Cardiology and MOH Key Laboratory of Thrombosis and Hemostasis, the First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
3Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, People's Republic of China.
4Department of Gerontology, the First Hospital of Yancheng, Yancheng, People's Republic of China.
5Molecular Cardiology, Cleveland Clinic, Cleveland, OH, USA.
摘要：
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.