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, Andersen Gitte, Kiess Wieland, Körner Antje, Kovacs Peter, Jacobson Peter, Carlsson Lena M S, Walley Andrew J, Jørgensen Torben, Hansen Torben, Pedersen Oluf, Meyre David, Froguel Philippe
Genomic Medicine, Imperial College London, Hammersmith Hospital, London W120NN, UK.
Nat Genet. 2008 Aug;40(8):943-5. doi: 10.1038/ng.177. Epub 2008 Jul 6.
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.
前蛋白转化酶枯草溶菌素1（PCSK1）基因突变会导致单基因肥胖。为评估PCSK1对多基因肥胖风险的影响，我们对来自八个独立病例对照或家系队列的总共13659名欧洲裔个体的标签单核苷酸多态性（tag SNPs）进行了基因分型。编码N221D的非同义变体rs6232以及编码Q665E-S690T对的rs6234-rs6235，在成人和儿童中均与肥胖持续相关（P值分别为7.27×10⁻⁸和2.31×10⁻¹²）。功能分析表明，N221D突变的PC1/3蛋白催化活性显著受损。
