LRP6 mutation in a family with early coronary disease and metabolic risk factors

被引：482

作者：

Mani, Arya ^{[1
]}

Radhakrishnan, Jayaram

Wang, He

Mani, Alaleh

Mani, Mohammad-Ali

Nelson-Williams, Carol

Carew, Khary S.

Mane, Shrikant

Najmabadi, Hossein

Wu, Dan

Lifton, Richard P.

机构：

[1] Howard Hughes Med Inst, Dept Internal Med, New Haven, CT 06510 USA

[2] Howard Hughes Med Inst, Dept Genet & Mol Biophys, New Haven, CT 06510 USA

[3] Howard Hughes Med Inst, Dept Biochem, New Haven, CT 06510 USA

[4] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA

[5] Amirkabir Univ Technol, Dept Mat Sci, Tehran 15875 4413, Iran

[6] Azad Univ Tehran, Dept Human Sci, Tehran 13185 786, Iran

[7] Social Welf & Rehab Sci Univ, Ctr Gene Res, Tehran 19875 383, Iran

来源：

SCIENCE | 2007年 / 315卷 / 5816期

关键词：

D O I：

10.1126/science.1136370

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Coronary artery disease ( CAD) is the leading cause of death worldwide and is commonly caused by a constellation of risk factors called the metabolic syndrome. We characterized a family with autosomal dominant early CAD, features of the metabolic syndrome (hyperlipidemia, hypertension, and diabetes), and osteoporosis. These traits showed genetic linkage to a short segment of chromosome 12p, in which we identified a missense mutation in LRP6, which encodes a co-receptor in the Wnt signaling pathway. The mutation, which substitutes cysteine for arginine at a highly conserved residue of an epidermal growth factor-like domain, impairs Wnt signaling in vitro. These results link a single gene defect in Wnt signaling to CAD and multiple cardiovascular risk factors.

引用

页码：1278 / 1282

页数：5

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