趋化因子受体6基因单核苷酸多态性与系统性红斑狼疮的相关性研究

发布时间：2018-06-16 00:52

  本文选题：系统性红斑狼疮 + 趋化因子受体6　； 参考：《安徽医科大学》2015年硕士论文

【摘要】：研究背景趋化因子受体6(chemokine receptor 6,CCR6)是一种多功能细胞因子受体。近年来年,国内外已有许多关于CCR6作用及其功能的研究,并已经证实CCR6与多种自身免疫性疾病的发病有关,如类风湿关节炎、银屑病、Graves’病、克罗恩病等。然而,CCR6与系统性红斑狼疮(systemic lupus erythematosus,SLE)的研究却很少,更未见其基因多态性与SLE易感性的研究。本研究从CCR6基因多态性的角度来探讨CCR6与SLE发病之间的关系,为进一步揭示SLE的发病机制提供理论依据。目的探讨CCR6基因单核苷酸多态性(single nucleotide polymorphism,SNP)与中国汉族人群SLE遗传易感性的关系,并分析其与SLE患者临床特征之间的关系。方法收集来自安徽医科大学第一附属医院和安徽省立医院两家医院风湿科门诊或住院部的SLE患者760例,对照来自于安徽医科大学健康志愿者和安徽医科大学第一附属医院健康体检中心体检人员,共761例。采用自行设计的调查问卷收集研究对象的一般人口学资料及有关临床资料,并采集静脉血3~5 ml。使用Taq Man基因分型技术,对SLE患者和正常对照进行CCR6基因rs3093024和rs1854853两个SNP位点基因分型,分析SLE患者和正常对照等位基因和基因型频率分布情况,并探讨CCR6基因多态性与SLE常见临床特征之间的关系。结果(1)CCR6基因rs3093024位点A和G等位基因频率在SLE组中分别为40.79%和59.21%,在对照组中分别为42.38%和57.62%,差异无统计学意义(?2=0.79,P=0.374)。基因型AA、AG和GG在SLE组中的频率分别为17.89%、45.79%和36.32%,在对照组中分别为18.13%、48.49%和33.38%,基因型与SLE发病之间未显示有统计学意义(?2=1.54,P=0.463)。遗传模型分析结果显示,显性模型(AA+AG vs.GG)、隐性模型(AA vs.GG+AG)与SLE易感性间均未见有统计学关联(均有P0.05)。CCR6基因rs1854853位点G和A等位基因频率在SLE组和对照组中相似,SLE组中G和A等位基因频率分别为49.34%和50.66%,对照组中分别为49.47%和50.53%,差异无统计学意义(?2=0.01,P=0.942)。GG、AG和AA 3种基因型的频率在病例组中分别为23.95%、50.79%和25.26%,对照组中这3种基因型的频率依次为24.70%、49.54%和25.76%,差异无统计学意义(χ2=0.24,P=0.885)。遗传模型分析结果显示,显性模型(GG+AG vs.AA)和隐性模型(GG vs.AA+AG)和SLE发病之间均未见有统计学关联(均有P0.05)。(2)CCR6基因rs3093024位点A等位基因可能为盘状红斑的保护因素。A等位基因相比于G等位基因,OR值为0.654(95%CI:0.447~0.958,P=0.028),同时,显性模型AA+AG相比于GG的OR值为0.539(95%CI:0.324~0.895,P=0.016)。结论CCR6基因rs3093024位点与SLE易感性无关,但与其并发临床症状盘状红斑有关;CCR6基因rs1854853位点与SLE发病及其临床特征均无关。
[Abstract]:Background chemokine receptor 6(chemokine receptor 6 (CCR 6) is a multifunctional cytokine receptor. In recent years, there have been many studies on the role and function of CCR6 at home and abroad, and it has been proved that CCR6 is associated with many autoimmune diseases, such as rheumatoid arthritis, psoriasis, Graves' disease, Crohn's disease and so on. However, there are few studies on CCR6 and systemic lupus erythematosus SLEs, and there are no studies on their gene polymorphisms and susceptibility to systemic lupus erythematosus. This study explored the relationship between CCR6 gene polymorphism and the pathogenesis of SLE in order to provide a theoretical basis for further revealing the pathogenesis of SLE. Objective to investigate the relationship between single nucleotide polymorphisms (SNPs) of CCR6 gene and the genetic susceptibility of Chinese Han population, and to analyze the relationship between CCR6 gene polymorphism and clinical features. Methods 760 SLE patients were collected from the first affiliated Hospital of Anhui Medical University and the Department of Rheumatology, Anhui Provincial Hospital. The control group consisted of 761 healthy volunteers from Anhui Medical University and a total of 761 medical examiners from the Health examination Center of the first affiliated Hospital of Anhui Medical University. The general demographics and clinical data of the subjects were collected by a self-designed questionnaire, and the venous blood was collected at 35 ml. Using Taq Man genotyping technique, CCR6 rs3093024 and rs1854853 loci were genotyped in patients with SLE and normal controls, and the distribution of alleles and genotypes in SLE patients and normal controls were analyzed. To explore the relationship between CCR6 gene polymorphism and common clinical features of SLE. Results the frequencies of A and G alleles at rs3093024 locus of CCR6 gene were 40.79% and 59.21% in SLE group, 42.38% and 57.62% in control group, respectively. The frequencies of AA AG and GG in SLE patients were 45.79% and 36.32, respectively, and those in the control group were 18.138.49% and 33.38%, respectively. There was no significant difference between genotype and SLE incidence. The results of genetic model analysis show that, No significant association was found between the dominant model AA AG vs.GG and the latent model AA vs.GG) and the susceptibility to SLE (P 0.05N. CCR6 allele G and A allele frequencies were found in similar SLE patients with SLE and control group.) there was no significant correlation between G and A allele frequencies in SLE patients and controls. 49.34% and 50.66% in the control group, 49.47% and 50.53% in the control group, respectively. There was no significant difference in the frequencies of the three genotypes (23.9595%, 50.79% and 25.26%, respectively). There was no significant difference in the frequencies of the three genotypes between the two groups (蠂 2 0.24 P 0. 885). The frequencies of the three genotypes in the control group were 24. 70% and 25. 76%, respectively (蠂 2 0.24 P 0. 88 5), and the frequencies of the three genotypes in the control group were 24. 70% and 25. 76%, respectively (蠂 2 0.24 P 0. 885). The results of genetic model analysis show that, There was no significant correlation between the dominant model (GG AG vs.AA) and the recessive model (GG vs.AA AGG) and the incidence of rs3093024 (P 0.05). The A allele of the CCR6 gene may be the protective factor of the disc erythema. The allele A was higher than the G allele (OR = 0.65495 CI: 0.4477.0.958) compared with the G allele. At the same time, there was no significant difference between the two alleles. The OR value of dominant model AA AG compared with GG was 0.539% 95% CI: 0.324% 0.89 5% Pao 0.016%. Conclusion CCR6 gene rs3093024 locus is not associated with susceptibility to SLE, but CCR6 gene rs1854853 locus is not associated with the pathogenesis and clinical characteristics of SLE.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R593.241
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本文编号：2024454