Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus
Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus
复制标题
DOI：
10.1093/hmg/11.5.589
复制
发表时间：
2002-03-01
影响因子：
3.5
通讯作者：
Kere, J
中科院分区：
文献类型：
--
作者：
Asumalahti, K;Veal, C;Kere, J
与HLA-C相似的PSORS 1是银屑病的主要遗传决定因素。我们目前的遗传和结构的证据表明，在PSORS 1位点的HCR基因的主要作用。来自6个人群的419个家族的基因分型显示，编码HCR的单核苷酸多态性形成了一个保守的等位基因HCR*WWCC，该等位基因在所有人群中与银屑病和HLA-Cw 6等位基因高度显著相关。由于HLA-Cw 6和HCR*WWCC之间存在很强的连锁不平衡，这两个基因在遗传学上无法通过这个样本量区分。然而，预测变体HCR等位基因在二级结构上不同于野生型蛋白。HCR蛋白在银屑病皮损中的表达与在正常皮肤中观察到的有很大不同。这些结果为HCR*WWCC等位基因可能通过影响角质形成细胞增殖的机制作为银屑病的主要遗传决定因素提供了强有力的证据。
PSORS1, near HLA-C, is the major genetic determinant of psoriasis. We present genetic and structural evidence suggesting a major role for the HCR gene at the PSORS1 locus. Genotyping of 419 families from six populations revealed that coding single-nucleotide polymorphisms of HCR formed a conserved allele HCR*WWCC that associated highly significantly with psoriasis and with the HLA-Cw6 allele in all populations. Because of strong linkage disequilibrium between HLA-Cw6 and HCR*WWCC, the two genes could not be genetically distinguished by this sample size. However, the variant HCR allele was predicted to differ in secondary structure from the wild-type protein. HCR protein expression in lesional psoriatic skin differed considerably from that observed in normal skin. These results provide strong evidence for the HCR*WWCC allele as a major genetic determinant for psoriasis, probably by a mechanism impacting on keratinocyte proliferation.