Sirois Francine, Kaefer Nadine, Currie Krista A, Chrétien Michel, Nkongolo Kabwe K, Mbikay Majambu
Chronic Disease Program, Ottawa Hospital Research Institute, 725 Parkdale Avenue, Ottawa, ON, K1Y 4E9, Canada.
J Community Genet. 2012 Oct;3(4):319-22. doi: 10.1007/s12687-012-0081-5. Epub 2012 Feb 4.
The PCSK1 (proprotein convertase subtilisin/kexin type 1) locus encodes proprotein convertase 1/3, an endoprotease that converts prohormones and proneuropeptides to their active forms. Spontaneous loss-of-function mutations in the coding sequence of its gene have been linked to obesity in humans. Minor alleles of two common non-synonymous single-nucleotide polymorphisms (SNPs), rs6232 (T > C, N221D) and rs6235 (C > G, S690T), have been associated with increased risk of obesity in European populations. In this study, we compared the frequencies of the rs6232 and rs6234 (G > C, Q665E) SNPs in Aboriginal and Caucasian populations of Northern Ontario. The two SNPs were all relatively less frequent in Aboriginals: The minor allele frequency of the rs6232 SNP was 0.01 in Aboriginals and 0.08 in Caucasians (P < 4.10(-6)); for the rs6234 SNP, it was 0.20 and 0.32, respectively (P < 0.001). Resequencing revealed that the rs6234 SNP variation was tightly linked to that of the rs6235 SNP, as previously reported. Most interestingly, all carriers of the rs6232 SNP variation also carried the rs6234/rs6235 SNP clustered variations, but not the reverse, suggesting the former occurred later on an allele already carrying the latter. These data indicate that, in Northern Ontario Aboriginals, the triple-variant PCSK1 allele is relatively rare and might be of lesser significance for obesity risk in this population.
PCSK1（前蛋白转化酶枯草杆菌蛋白酶/kexin 1型）基因座编码前蛋白转化酶1/3，这是一种将激素原和神经肽原转化为其活性形式的内肽酶。其基因编码序列中的自发功能丧失突变与人类肥胖有关。两种常见的非同义单核苷酸多态性（SNP），即rs6232（T＞C，N221D）和rs6235（C＞G，S690T）的次要等位基因，与欧洲人群肥胖风险增加有关。在本研究中，我们比较了安大略省北部原住民和白种人群体中rs6232和rs6234（G＞C，Q665E）SNP的频率。这两个SNP在原住民中的频率都相对较低：rs6232 SNP的次要等位基因频率在原住民中为0.01，在白种人中为0.08（P＜4.10⁻⁶）；对于rs6234 SNP，分别为0.20和0.32（P＜0.001）。重测序显示，rs6234 SNP变异与rs6235 SNP变异紧密连锁，如先前报道。最有趣的是，rs6232 SNP变异的所有携带者也携带rs6234/rs6235 SNP簇状变异，但反之则不然，这表明前者是在已经携带后者的等位基因上后来发生的。这些数据表明，在安大略省北部原住民中，三变异PCSK1等位基因相对罕见，可能对该人群的肥胖风险影响较小。
