内质网氨基肽酶1基因rs27044、rs30187和rs26653多态性与汉族寻常性银屑病相关性研究

Association of rs27044, rs30187 and rs26653 single nucleotide polymorphisms in the endoplasmic reticulumaminopeptidase 1 gene with psoriasis vulgaris in a Chinese Han population

目的探讨内质网氨基肽酶1（ERAP1）基因多态性与汉族人寻常性银屑病的遗传关联性。方法收集寻常性银屑病患者289例，对照组292例，知情同意后采集外周静脉血5ml。选择位于ERAP1基因编码区域的3个单核苷酸多态性（SNP），利用连接酶检测反应进行基因分型（rs27044、rs30187和rs26653）。利用PLINK1．07软件进行统计分析，r检验比较患者组与对照组等位基因频率及基因型频率，计算等位基因的相对危险度估计值比值比（OR）及其95％可信区间（95％C1）。利用Haploview软件进行单倍型分析。结果rs30187等位基因C及rs26653等位基因G在患者组的频率（分别为0．4602和0．4308）、尤其是早发型组中的频率（0．4485和0．4227）均明显低于对照组（0．5342和0．5017），差异均有统计学意义（均P〈0．05）。rs27044、rs30187及rs26653这3个SNP两两间均存在强连锁不平衡（r2≥0．717，D’≥0．962）。基因型分析结果显示，在隐．f生遗传模式下，rs30187在患者组及早发型组的基因型频率均显著低于对照组，差异均有统计学意义（P值分别〈0．05和〈0．0167）。单倍型分析发现，单倍型（H4：CTC）在患者组的频率（0．050）、尤其是早发型组的频率（0．052）均明显高于对照组（0．022），差异均有统计学意义（P值分别〈0．05、〈0．0167）。结论ERAP1基因多态性与汉族人寻常性银屑病可能相关，特别是早发型患者。危险单倍型（H4：CTC）可能是寻常性银屑病一个重要的易感因素。

Objective To investigate the association between endoplasmic reticulum aminopeptidase 1 （ERAP1） gene polymorphisms and psoriasis vulgaris （PsV） in a Chinese Han population. Methods Five milliliters of venous blood samples were collected from 289 patients with PsV and 292 human controls of Han nationality after informed consent. Three single nucleotide polymorphisms （SNPs） in the encoding area of the ERAP1 gene, including rs27044, rs30187 and rs26653, were genotyped by ligase detection reaction （LDR）. With the PLINK 1.07 package, statistical analysis was carried out by using the chi-square test for comparisons of allele and genotype frequencies between the patient group and control group. The allelie odds ratio （OR） and its 95% confidence interval （CI） were calculated. In addition, haplotype analysis was conducted with the Haploview software. Results The frequencies of rs30187_C and rs26653_G alleles were significantly lower in the patient group （0.460 2 and 0.430 8 respectively）, especially in patients with early-onset PsV （0.448 5 and 0.422 7 respectively）, than in the control group （0.534 2 and 0.501 7 respectively, all P〈 0.05）. The SNPs rs27044, rs30187 and rs26653 showed strong linkage disequilibrium with each other （r2〉 0.717, D＇ /〉 0.962）. Genotype analysis showed that the frequency of the rs30187 CC genotype was significantly lower in the patient group, especially in patients with early-onset PsV, than in the control group （P 〈 0.05 and 0.016 7 respectively） under arecessive mode of inheritance. Haplotype analysis revealed that the frequency of the haplotype H4： CTC was significantly increased in the patient group （0.050）, especially in patients with early-onset PsV （0.052）, compared with the control group （0.022, P〈 0.05 and 0.016 7 respectively）. Conclusions ERAP1 gene polymorphisms are associated with PsV, especially with early-onset PsV in Chinese Han population. The risk haplotype H4： CTC may be a susceptible factor for PsV.