Stijnen Pieter, Tuand Krizia, Varga Tibor V, Franks Paul W, Aertgeerts Bert, Creemers John W M
Am J Epidemiol. 2014 Dec 1;180(11):1051-65. doi: 10.1093/aje/kwu237. Epub 2014 Oct 29.
Congenital deficiency of the proprotein convertase subtilisine/kexin type 1 gene (PCSK1), which encodes proprotein convertase 1/3, causes a severe multihormonal disorder marked by early-onset obesity. The single nucleotide polymorphisms (SNPs) rs6232 and rs6234-rs6235 in PCSK1 have been associated with obesity. However, case-control studies carried out in populations of different ethnicities have only partly replicated this association. Moreover, these SNPs have only weakly been associated with body mass index (weight (kg)/height (m)(2)) at a genome-wide level of significance. To investigate this discrepancy, we conducted a systematic search for studies published before December 2013 and extracted relevant data. Pooled estimates were calculated for overall and subgroup analyses. This meta-analysis confirmed the association of PCSK1 SNPs with obesity and provides the first evidence that the association between PCSK1 rs6232 and obesity is stronger for childhood obesity than for adult obesity. Moreover, we identified weak associations with body mass index and significantly stronger associations with waist circumference for rs6234-rs6235. No difference was found in the association with different obesity grades, and no association of PCSK1 rs6234-rs6235 with obesity was identified in Asian populations. This systematic Human Genome Epidemiology (HuGE) review showed convincingly that the SNPs rs6232, rs6234, and rs6235 in PCSK1 are associated with obesity in Caucasians.
前蛋白转化酶枯草杆菌蛋白酶/kexin 1型基因（PCSK1）先天性缺陷可导致严重的多激素紊乱，并伴有早发性肥胖。PCSK1基因编码前蛋白转化酶1/3。PCSK1基因中的单核苷酸多态性（SNP）rs6232以及rs6234 - rs6235与肥胖有关。然而，在不同种族人群中开展的病例对照研究仅部分重复了这种关联。此外，在全基因组显著水平上，这些SNP与体重指数（体重（千克）/身高（米）²）的关联较弱。为了探究这一差异，我们对2013年12月之前发表的研究进行了系统检索，并提取了相关数据。计算了合并估计值用于总体分析和亚组分析。这项荟萃分析证实了PCSK1基因SNP与肥胖之间的关联，并首次提供证据表明，PCSK1基因rs6232与肥胖之间的关联在儿童肥胖中比在成人肥胖中更强。此外，我们发现rs6234 - rs6235与体重指数存在弱关联，与腰围的关联则显著更强。在与不同肥胖等级的关联中未发现差异，并且在亚洲人群中未发现PCSK1基因rs6234 - rs6235与肥胖有关联。这项系统性人类基因组流行病学（HuGE）综述令人信服地表明，PCSK1基因中的SNP rs6232、rs6234和rs6235与高加索人群的肥胖有关。
