Common nonsynonymous variants in PCSK1 confer risk of obesity.

Authors :: Benzinou M
Creemers JW
Choquet H
Lobbens S
Dina C
Durand E
Guerardel A
Boutin P
Jouret B
Heude B
Balkau B
Tichet J
Marre M
Potoczna N
Horber F
Le Stunff C
Czernichow S
Sandbaek A
Lauritzen T
Borch-Johnsen K
Andersen G
Kiess W
Körner A
Kovacs P
Jacobson P
Carlsson LM
Walley AJ
Jørgensen T
Hansen T
Pedersen O
Meyre D
Froguel P
Source :: Nature genetics [Nat Genet] 2008 Aug; Vol. 40 (8), pp. 943-5. Date of Electronic Publication: 2008 Jul 06.
Publication Year :: 2008
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 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.