白介素22（IL-22）基因拷贝数变异与中国汉族强直性脊柱炎的相关性研究

发布时间：2018-05-05 01:24

  本文选题：强直性脊柱炎 + 白介素22拷贝数变异　； 参考：《安徽医科大学》2017年硕士论文

【摘要】：目的:1.描述白介素22(interleukin 22,IL-22)基因拷贝数在中国汉族强直性脊柱炎(Ankylosing Spondylitis,AS)患者以及正常人群的分布情况;2.分析IL-22基因拷贝数变异(Copy Number Variations,CNVs)与AS遗传易感性之间的关联;3.探讨IL-22 CNVs与AS的疾病严重程度是否存在相关性,同时研究与IL-22CNVs在疾病发生发展过程中有交互作用的环境因素,为进一步阐明AS的发病机制提供线索。方法:1.共收集2013-2016年间就诊于安徽医科大学第一附属医院风湿免疫科的AS患者649例,按性别、年龄匹配的原则收集来自合肥市中心血站的健康志愿者为对照,共628例。抽取患者和健康对照外周血标本5ml,同时用本课题组设计的流行病学调查表收集所有研究对象的一般人口学资料,以及患者的实验室指标,临床特征资料等。2.采用DNA试剂盒(QIAGEN)提取AS病人及健康对照的DNA样本,放于-80℃冰箱存放,最后应用AccuCopy~(TM)多重基因拷贝数检测技术测定IL-22基因拷贝数。3.两组间定量资料的比较采用t检验,定性资料的比较以及IL-22拷贝数在两组间分布情况分析采用χ~2检验,回归模型用来分析CNVs与疾病严重程度的关联,CNVs与环境因素交互作用的分析采用单纯病例研究。所有的统计分析在SPSS16.0中进行,P0.05被认为有统计学意义。结果:1.IL-22基因拷贝数在中国汉族AS患者和健康对照中的分布及比较:IL-22_1基因拷贝数有1和2,在AS患者中,1拷贝有4例(0.6%),2拷贝有626例(99.4%);对照组中,1拷贝有3例(0.5%),2拷贝有592例(99.5%);IL-22_2基因拷贝数范围为1~3,病例组中,1拷贝有7例(1.1%),2拷贝有612例(98.6%),3拷贝有2例(0.3%);而对照组中,1拷贝有19例(3.2%),2拷贝有573例(96.8%),3拷贝有0例(0%)。IL-22_1拷贝数分布在病例组和对照组中差异无统计学意义(χ~2=0.092,P=1.000),而IL-22_2拷贝数在两组间分布差异有统计学意义(χ~2=7.760,P=0.01)。考虑到IL-22_2基因3拷贝的变异频率过低,仅0.3%,且在对照中未检测到,对其剔除后,IL-22_2基因1拷贝和2拷贝在两组间分布差异仍有统计学意义(χ~2=6.223,P=0.013)。按性别分组后,在男性中差异有统计学意义(χ~2=6.894,P=0.009)。2.IL-22基因拷贝数变异与AS疾病严重程度的关联性分析:回归分析法未发现IL-22拷贝数变异与疾病活动度(Bath Ankylosing Spondylitis Disease Activity Index,BASDAI)以及疾病功能指数(Bath Ankylosing Spondylitis Functional Index,BASFI)有关联。3.IL-22_2基因拷贝数变异与环境交互作用的分析:偶尔食用蔬菜的病人与经常食用的病人相比,基因环境交互作用为OR=8.93,95%CI=1.21-65.81,P=0.032,其他环境因素未发现与IL-22_2基因CNVs存在交互作用。结论:IL-22基因CNVs可能与AS易感性有关,低拷贝数(=1)可能是AS发病的保护因素;IL-22基因CNVs不会影响AS的疾病严重程度;而基因环境交互作用分析发现,食用蔬菜情况可能与IL-22基因拷贝数变异相互作用共同影响AS的发病。
[Abstract]:Purpose 1. To describe the distribution of interleukin-22 (IL-22) gene copy number in patients with ankylosing spondylitis (Ankylosing Spondylitis) and normal population in Chinese Han nationality. To analyze the association between copy Number variation (IL-22) and as genetic susceptibility. To explore the correlation between IL-22 CNVs and as severity, and to study the environmental factors that interact with IL-22CNVs in the process of disease development, and to provide clues for further elucidating the pathogenesis of as. Method 1: 1. A total of 649 patients with as from the Department of Rheumatology and Immunology, first affiliated Hospital of Anhui Medical University, were collected from 2013 to 2016. 628 healthy volunteers from Hefei Central Blood Station were collected as controls according to the principle of gender and age matching. The peripheral blood samples of patients and healthy controls were collected from 5 ml, and the general demographic data of all subjects were collected with the epidemiological questionnaire designed by our research group, as well as the laboratory indexes and clinical characteristics of patients. DNA samples from as patients and healthy controls were extracted by DNA kit QIAGEN and stored in a refrigerator at -80 鈩，

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