학술논문
Common nonsynonymous variants in PCSK1 confer risk of obesity.
Document Type
Article
Author
Benzinou, Michael; Creemers, John W. M.; Choquet, Helene; Lobbens, Stephane; Dina, Christian; Durand, Emmanuelle; Guerardel, Audrey; Boutin, Philippe; Jouret, Beatrice; Heude, Barbara; Balkau, Beverley; Tichet, Jean; Marre, Michel; Potoczna, Natascha; Horber, Fritz; Le Stunff, Catherine; Czernichow, Sebastien; Sandbaek, Annelli; Lauritzen, Torsten; Borch-Johnsen, Knut
Source
Subject
*GENETIC research
*OBESITY risk factors
*GENETICS of childhood obesity
*METABOLIC disorders
*FUNCTIONAL analysis
*
*
*
*
Language
ISSN
1061-4036
Abstract
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 × 10−8 and P = 2.31 × 10−12, respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity. [ABSTRACT FROM AUTHOR]