转录因子和转录激活因子4人细胞毒性T淋巴细胞相关抗原-4和染色体9p21．3遗传多态性与闽南地区人群类风湿关节炎相关性研究  

Association of genetic polymorphisms of STAT4, the cytotoxic T-lymphocyte antigen-4 and chromo- some 9p21.3 with susceptibility to rheumatoid arthritis in Minnan population

作　　者：郑晨娜[1] 饶华春 罗彩林[1] 王清瑶 杨会勇[3] 刁勇[3] 

机构地区：[1]泉州医学高等专科学校基础医学部,362000 [2]福建省泉州市正骨医院临床检验科 [3]华侨大学生物医学学院分子药物研究院

出　　处：《中华风湿病学杂志》2016年第6期372-377,共6页Chinese Journal of Rheumatology

基　　金：国家自然科学基金（31200979）;福建省自然科学基金（2015J01138）;福建省卫生厅青年基金（2012-2-118）;福建省泉州市技术研究与开发重点项目（2011230）;华侨大学中青年教师科技创新资助计划（ZQN-PY319）.

摘　　要：目的探讨转录因子和转录激活因子4（STAT4）rs7574865、人细胞毒性T淋巴细胞相关抗原-4（CTLA-4）rs3087243基因以及染色体9p21.3 rs1333049单核苷酸多态性（SNPs）与闽南地区人群RA的关联。方法选取119例RA患者和125名健康对照者，应用三引物扩增法（AS-PCR）对RA相关的3个SNPs位点进行基因分型，并应用SPSS 18.0统计软件分析不同基因型与RA发病的相关性。采用χ2检验和Logistic回归模型进行分析。结果RA组STAT4 rs7574865各基因型分布频率与健康对照组比较，差异有统计学意义（P〈0.01），与G/T杂合基因型相比，TT与GG纯合性携带者患病风险要低（OR=0.498和0.300，P=0.018和P=0.002）；CTLA-4 rs3087243各基因型分布频率与健康对照组比较，差异无统计学意义（χ^2=4.083，P=0.130），但根据计算，其中与A/G基因型相比，GG型携带者患病风险要低（OR=0.580，P=0.04）；9p21.3上的SNP（rs1333049）无论基因型还是等位基因在RA与健康志愿者组间差异无统计学意义，但是经计算发现与GG基因型携带者相比，CC和GC携带者发病风险要低（OR=0.565，P=0.049 5）。结论STAT4 rs7574865和CTLA-4 rs3087243和rs1333049与闽南地区人群RA发病均有一定相关性。Objective A very high prevalence of rheumatoid arthritis （RA） is observed in Minnan population in China. We aimed to explore the genetic characteristics of RA in Minnan population and genetic mechanisms of RA by studying the associations of three single nucleotide polymorphisms （SNPs） of signal transducer and activator of transcription 4 （STAT-4） （rs7574865）, the cytotoxic T-lymphocyte antigen-4 （CTLA）-4 （rs3087243） and chromosome 9p21.3（rs1333049） with RA in Minnan population.Methods A case-control study of 119 RA patients and 125 normal controls from Quanzhou were enrolled. SNPs （rs7574865, rs3087243, rs1333049） were genotyped by allele-specific polymerase chain reaction （PCR） and analyzed by SPSS 18.0. χ^2-test was applied to compare allele and genotype frequeneies betweeen cases and controlsLogistic regression models were used to analyze the SNPs.Results The results showed the genotype distributions of STAT4 genes were significantly different between case and control groups （P〈0.01）. Compared with the GT heterozygous genotype, TT and GG homozygosity carriers had a lower risk（OR=0498 and 0.300, P=0.018 and P=0.002 respectively）. There was not statistical difference in genotypes and allele in CTLA-4 （rs3087243） between RA patients and healthy controls （χ^2=4.083, P=0.130）, but compared with the AG genotyoe, GG homozygosity carriers had a lower risk on basis of statistics （OR=0.580, P=0.04）. There was not statistical difference in genotypes and allele in the chromosome 9p21.3 （rs1333049） （P〉0.05）, but compared with the GG genotype carriers, CC and GC genotypes carriers had a lower risk on basis of statistics （OR=0.565, P=0.0495）.Conclusion Chromosome 9p21.3 （rs1333049） and CTLA-4 rs3087243 G/A may not be associated with susceptibility to RA in Minnan populations. This replication study confirmes that STAT4 rs7574865 G/T polymorphism is associated with susceptibility to RA in Minnan population.

关 键 词：关节炎 类风湿 多态性 单核苷酸 转录因子和转录激活因子4 人细胞毒性T淋巴细胞相关抗原-4 染色体9p21.3 

分 类 号：R593.22[医药卫生—内科学]