Genetic polymorphism of rs9277535 in HLA-DP associated with rheumatoid arthritis and anti-CCP production in a Chinese population
Genetic polymorphism of rs9277535 in HLA-DP associated with rheumatoid arthritis and anti-CCP production in a Chinese population
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中国人群 HLA-DP rs9277535 基因多态性与类风湿性关节炎及抗 CCP 产生相关
DOI：
10.1007/s10067-018-4030-5
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发表时间：
2018-07-01
影响因子：
3.4
通讯作者：
Wang, Lanlan
中科院分区：
文献类型：
--
作者：
Huang, Zhuochun;Niu, Qian;Wang, Lanlan
HLA-II分子在触发人类免疫应答，特别是在活化CD 4 + T细胞中是至关重要的。HLA-DP属于HLA-II类分子，其在病毒抗原和自身抗原呈递给T细胞中的作用日益受到关注。已有研究报道HLA-DP单核苷酸多态性（single nucleotide polymorphism，SNP）与HBV感染及SLE等自身免疫性疾病相关。然而，HLA-DP与类风湿关节炎（RA）的关系却知之甚少。Rs 9277535位于HLA-DP亚基HLA-DPB 1的3′ UTR区，影响HLA-DP mRNA的表达。本研究旨在探讨HLA-DPB 1基因rs 9277535多态性与RA易感性及进展的关系。收集了254例RA患者和391例年龄和性别匹配的健康对照的样本，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。通过实验室检测血清学检查（抗CCP、类风湿因子、C反应蛋白、抗角蛋白抗体）。HLA-DP基因rs 9277535多态性与RA易感性密切相关（等位基因频率分布：OR = 1.409，95%CI = 1.121- 1.773，P = 0.004）。疾病模型分析（隐性模型：OR = 1.889，95%CI = 1.194- 2.990，P = 0.008;显性模型：OR = 1.464，95%CI = 1.050- 2.041，P = 0.025;加性模型：OR = 2.208，95%CI = 1.335- 3.652，P = 0.003）进一步验证了上述结果。等位基因A与RA风险增加相关。血清学检测结果显示携带rs 9277535等位基因A的患者血清抗CCP抗体水平升高。本研究为HLA-DP基因多态性与RA易感性相关提供了证据。HLA-DP基因rs 9277535等位基因A与RA发病风险增加及血清抗CCP抗体水平升高相关。
HLA-II molecules are critical in triggering human immune response, especially in activating CD4+ T cells. HLA-DP, belonging to HLA-II molecules, draws increasing attention for its role in presentation of viral antigen and autoantigen to T cells. Researches reported single nucleotide polymorphism (SNP) of HLA-DP associated with HBV infection and autoimmune diseases such as SLE. However, little is known about the relationship between HLA-DP and rheumatoid arthritis (RA). Rs9277535 is located in 3′ UTR region of HLA-DPB1, a subunit of HLA-DP, and was reported to affect HLA-DP mRNA expression. In the present study, we explored the relationship between gene polymorphism of rs9277535 in HLA-DPB1 and RA susceptibility and progression. Samples from 254 patients with RA and 391 age- and sex-matched healthy controls were collected and genotyped by a polymerase chain reaction-high-resolution melting (PCR-HRM) assay. Serological tests (anti-CCP, rheumatoid factor, C-reactive protein, anti-keratin antibody) were detected by laboratory assays. Strong association was observed between SNP rs9277535 in HLA-DP and RA susceptibility (allele frequency distribution: OR = 1.409, 95%CI = 1.121–1.773,P= 0.004). Further validation was provided by disease model analysis (recessive model: OR = 1.889, 95%CI = 1.194–2.990,P= 0.008; dominant model: OR = 1.464, 95%CI = 1.050–2.041,P= 0.025; additive model: OR = 2.208, 95%CI = 1.335–3.652,P= 0.003). Allele A was correlated to increased risk of RA. Serological test results demonstrated patients carrying allele A of rs9277535 had elevated serum anti-CCP antibody level. The present study provided evidence that HLA-DP gene polymorphism associated with RA susceptibility. Allele A of rs9277535 in HLA-DP correlated to increased risk of RA and elevated serum anti-CCP level.