Common nonsynonymous variants in PCSK1 confer risk of obesity
Common nonsynonymous variants in PCSK1 confer risk of obesity
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DOI：
10.1038/ng.177
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发表时间：
2008-08-01
期刊：
影响因子：
30.8
通讯作者：
Froguel, Philippe
中科院分区：
文献类型：
--
作者：
Benzinou, Michael;Creemers, John W. M.;Froguel, Philippe
PCSK1 突变会导致单基因肥胖。为了评估 PCSK1 对多基因肥胖风险的影响，我们对来自 8 个独立病例对照或基于家庭的队列的总共 13,659 名欧洲血统个体的标签 SNP 进行了基因分型。编码N221D的非同义变体rs6232和编码Q665E-S690T对的rs6234-rs6235与成人和儿童的肥胖一致相关（分别为P = 7.27 x 10(-8)和P = 2.31 x 10(-12)）。功能分析显示 N221D 突变体 PC1/3 蛋白催化活性显着受损。
Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity.