信号传导和转录活化因子-4的单核苷酸多态性与中国汉族人类风湿关节炎的相关性研究

Association of variants in signal transducerand activator of transcription 4 in Chinese Han population with rheumatoid arthritis

目的分析中国汉族人群信号传导和转录活化因子-4（STAT4）基因的单核苷酸多态性（SNPs），探讨其与RA易感性之间的关系。方法利用HapMap中国汉族人（CHB）数据，选择STAT4基因的标签SNPs（r2=0．9）。在228例RA患者和228名健康对照中，用多重PCR（iPLEX）和基质辅助激光解吸电离飞行时间质谱法（MALDI-TOFMS），对STAT4基因的23个SNPs位点进行基因分型。使用X2和Fisher确切概率法检验分析是否符合HaZy—Weinberg平衡，各基因型及等位基因频率比较采用，检验，所用软件为Haploview4．1软件。结果所检测的STAT4的多态性位点中，有3个SNPs位点rs11685878、rs12988825和r816833437的等位基因频率在2组间的差异有统计学意义（x2=6．0148，4．0248，5．5391，P〈0．05）。有3个位点rs11685878,rs16833437和rs12988825的基因型频率在2组间的差异有统计学意义（x2=6．8149，6．0987，6．6917，P〈0．05）。结论STAT4基因的多个SNPs位点的等位基因频率或基因型频率与中国汉族RA之间存在相关性。

Objective To investigate the associations of variants in signal transducer and activator of transcription 4 （STAT4） in Chinese Han population with rheumatoid arthritis （RA）.Methods The study was performed in 228 RA cases and 228 controls. Haplotypes from the HapMap database Chinese population were used to select tag-single-nucleotide polymorphisms （SNPs） （r2=0.9） in STAT4 gene. Twenty-three SNPs located in STAT4 gene were examined by multiplex polymerase chain reaction （PCR） and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry （MALDI-TOF MS）. The Hardy-Weinberg equilibrium （HWE） was tested by a chi-square and Fisher＇s analysis. Differences in genotypes of the STAT4 polymorphism variants were evaluated using a Chi-square test. All statistical analyses were done with Haploview 4.1 software. Results Significant difference was detected in three SNPs （rs11685878. rs129888 and rs16833437） in allele frequencies analysis （x2=6.014 8, 4.024 8, 5.539 1, P〈0.05）. Association was detected for three SNPs （rs11685878, rs16833437 and rs12988825） in genotype analysis （x2=6.814 9, 6.098 7, 6.691 7, P〈0.05）. Conclusion STAT4 may associate with susceptibility in Chinese Han population.