HCR基因的遗传多态性以及与HLA - C紧密相邻的一个基因组片段与台湾地区的银屑病患者相关。

Genetic polymorphisms of the HCR gene and a genomic segment in close proximity to HLA-C are associated with patients with psoriasis in Taiwan.

作者信息

Chang Y T, Shiao Y M, Chin P J, Liu Y L, Chou F C, Wu S, Lin Y F, Li L H, Lin M W, Liu H N, Tsai S F

机构信息

Department of Dermatology, National Yang-Ming University, Taipei, Taiwan, Republic of China.

出版信息

Br J Dermatol. 2004 Jun;150(6):1104-11. doi: 10.1111/j.1365-2133.2004.05972.x.

DOI:10.1111/j.1365-2133.2004.05972.x

PMID:15214895

Abstract

BACKGROUND

Although psoriasis vulgaris (PV) is strongly associated with HLA-Cw0602, it has been proposed that the association of Cw0602 is due to linkage disequilibrium and that other nearby genes are involved in PV susceptibility. The alpha-helix coiled-coil rod homologue (HCR) gene, located 110 kb telomeric to the HLA-C locus, is presumed to be one of the PV candidate genes. Recently, a 10-kb genomic segment, centromeric to HLA-C, defined by two new single nucleotide polymorphisms (SNPs) n.7A and n.9C, was found to have a stronger association with psoriasis than the HCR gene. Until now, no study of the association of the HCR gene, SNPs n.7, and n.9 has been conducted on Chinese patients with psoriasis.

OBJECTIVES

We aimed to determine whether the genetic polymorphisms of the HCR gene, SNPs n.7A, and n.9C were associated with an increased risk of psoriasis in Chinese patients.

METHODS

Using direct sequencing of the HCR gene and the genomic region containing SNPs n.7 and n.9, we investigated the HCR gene, SNPs n.7, and n.9 for disease association in 115 Chinese patients with psoriasis and 103 control subjects. The HCR SNPs were confirmed by denaturing high performance liquid chromatography. Genotyping for HLA-Cw*0602 was also carried out using sequence-based typing.

RESULTS

We observed a different allelic distribution between patient and control groups at nucleotide positions 386, 404, 1802 and 2406 of the HCR gene, and SNPs n.7, and n.9. The associations were much stronger in early onset PV patients (for HCR-386T and HCR-404T, odds ratio = 5.63, Pc < 0.0001). The HLA-Cw0602 also displayed a similar association with PV (odds ratio = 5.4, Pc < 0.0001). Moreover, SNP n.7A, SNP n.9C, Cw0602, HCR-386T, HCR-404T and HCR-1802T were in linkage disequilibrium with each other. Haplotype-based association analysis showed SNP n.7A-SNP n.9C-Cw0602-HCR-386T-HCR-404T-HCR-1802T-HCR-2406G as a major susceptibility haplotype in this Chinese population (for early onset patients, odds ratio = 5.15, Pc < 0.0001).

CONCLUSIONS

Our results indicate that the HCR gene, SNP n.7A, and SNP n.9C as well as Cw*0602 are major susceptibility markers for psoriasis in Chinese patients.

摘要

背景

虽然寻常型银屑病（PV）与HLA - Cw0602密切相关，但有人提出Cw0602的关联是由于连锁不平衡，且其他附近基因也参与了PV易感性。位于HLA - C基因座端粒方向110 kb处的α - 螺旋卷曲螺旋杆同源物（HCR）基因被认为是PV候选基因之一。最近，发现由两个新的单核苷酸多态性（SNP）n.7A和n.9C定义的、位于HLA - C着丝粒方向的一个10 kb基因组片段与银屑病的关联比HCR基因更强。到目前为止，尚未对中国银屑病患者进行HCR基因、SNP n.7和n.9的关联研究。

目的

我们旨在确定HCR基因、SNP n.7A和n.9C的基因多态性是否与中国银屑病患者患银屑病风险增加相关。

方法

通过对HCR基因以及包含SNP n.7和n.9的基因组区域进行直接测序，我们在115例中国银屑病患者和103例对照受试者中研究了HCR基因、SNP n.7和n.9与疾病的关联性。通过变性高效液相色谱法确认HCR SNP。还使用基于序列的分型方法对HLA - Cw*0602进行基因分型。

结果

我们观察到HCR基因的第386、404、1802和2406位核苷酸位置以及SNP n.7和n.9在患者组和对照组之间存在不同的等位基因分布。在早发型PV患者中这种关联更强（对于HCR - 386T和HCR - 404T，优势比 = 5.63，Pc < 0.0001）。HLA - Cw0602与PV也显示出类似的关联（优势比 = 5.4，Pc < 0.0001）。此外，SNP n.7A、SNP n.9C、Cw0602、HCR - 386T、HCR - 404T和HCR - 1802T彼此处于连锁不平衡状态。基于单倍型的关联分析显示SNP n.7A - SNP n.9C - Cw0602 - HCR - 386T - HCR - 404T - HCR - 1802T - HCR - 240,6G是该中国人群中的主要易感单倍型（对于早发型患者，优势比 = 5.15，Pc < 0.0001）。