Genetic Polymorphisms of rs3077 and rs9277535 in HLA-DP associated with Systemic lupus erythematosus in a Chinese population.
Genetic Polymorphisms of rs3077 and rs9277535 in HLA-DP associated with Systemic lupus erythematosus in a Chinese population.
复制标题
中国人群系统性红斑狼疮相关HLA-DP rs3077和rs9277535基因多态性
DOI：
10.1038/srep39757
复制
发表时间：
2017-01-17
影响因子：
4.6
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Zhang J;Zhan W;Yang B;Tian A;Chen L;Liao Y;Wu Y;Cai B;Wang L
近年来，虽然在主要组织相容性复合体（MHC）区域内的HLA-DR和HLA-DQ基因位点已逐渐被全基因组关联研究（GWAS）所揭示，但HLA-DP多态性与SLE的相关性报道甚少。考虑到HLA-DP区域rs3077和rs 9277535的变异可能通过影响HLA Ⅱ类分子对CD 4 +T细胞的抗原提呈而影响免疫应答，本研究旨在探讨HLA-DP基因多态性在SLE发病中的作用。共收集了335例SLE患者和635例健康对照的样本，并通过聚合酶链反应-高分辨率熔解（PCR-HRM）分析进行基因分型。HLA-DP基因rs3077、rs 9277535与SLE易感性呈正相关（rs3077，OR = 0.74，95%CI = 0.60- 0.91，P = 0.004; rs 9277535，OR = 0.72，95%CI = 0.59- 0.88，P = 0.001）。Rs3077基因多态性与IL-17、INF-γ和皮肤血管炎相关（分别为P= 0.037、P = 0.020和P = 0.006）。此外，rs3077 AA基因型携带者比其他两种基因型表现出更低的炎性细胞因子浓度和更低的皮肤血管炎发病率。在rs 9277535和细胞因子或任何临床特征之间未观察到显著关联。结论：HLA-DP基因多态性（rs3077和rs 9277535）与SLE易感性及部分炎性细胞因子水平相关。
Although the SLE risk gene loci ofHLA-DRandHLA-DQwithin the major histocompatibility complex (MHC) region has been gradually revealed by recent Genome-Wide Association studies (GWAS), the association ofHLA-DPpolymorphisms with SLE was minimally reported. Considering that the variants in rs3077 and rs9277535 in theHLA-DPregion could influence the immune response by affecting antigen presentation of HLA class II molecules to CD4+T cells, the present study aimed to explore the role ofHLA-DPpolymorphisms in SLE. In total, samples from 335 SLE patients and 635 healthy controls were collected and genotyped by a polymerase chain reaction-high resolution melting (PCR-HRM) assay. A significant positive correlation was observed between the SNP rs3077, rs9277535 ofHLA-DPand SLE susceptibility (rs3077, OR = 0.74, 95%CI = 0.60–0.91,P= 0.004; rs9277535, OR = 0.72, 95%CI = 0.59–0.88,P= 0.001). Rs3077 polymorphism was corelated to IL-17, INF-γ and cutaneous vasculitis (P= 0.037,P= 0.020 andP= 0.006, respectively). Additionally, rs3077 AA genotype carriers showed lower concentration of inflammatory cytokines and lower cutaneous vasculitis incidence than did the other two genotype. No significant association was observed between rs9277535 and cytokines or any clinical features. In conclusion,HLA-DPpolymorphisms (rs3077 and rs9277535) were associated with SLE susceptibility and the levels of some inflammatory cytokines in SLE patients.