STAT4基因单核苷酸多态性与云南汉族人群SLE发病的相关性研究

Association Study of Single Nucleotide Polymorphism in STAT4 and Systemic Lupus Erythematosus in the Han Population of Yunnan Province

目的研究云南地区汉族人群STAT4基因单核甘酸多态性(SNP),探讨其与SLE疾病的易感性.方法结合国内外全基因组关联分析数据及本课题组前期研究结果,采用Sequenom MassArray质谱阵列技术对378例SLE患者和389例正常对照进行SATA4基因(rs10168266,rs10181656,rs11889341,rs13017460,rs1551443,rs16833249,rs2459611,rs3024879,rs3024886,rs3024894,rs3024895,rs3024933,rs3821236,rs4555370,rs6712821,rs7568275,rs7574865,rs7599504,rs8179673,rs932169)20个位点的基因分型.结果(1)STAT4的6个SNP等位基因频率在云南人群SLE患者和正常对照组之间的差异有统计学意义(P<0.05),并以rs10181656最为显著(P=5.41E-09),且相关程度较欧洲人群高;(2)对STAT4的SNP位点rs10181656进行分层分析,病例组中的蝶型红斑、粘膜溃疡、血液改变、肾损害、抗ds-DNA、ANA和浆膜炎与对照组之间G等位基因频率比较分布均有统计学意义(P<0.01).结论 STAT4基因多态性与云南汉族人系统性红斑狼疮易感性相关;STAT4基因rs10181656 G等位基因增加了SLE病人发生关节炎、蝶型红斑、肾损害、粘膜溃疡、抗ds-DNA、ANA、血液改变、浆膜炎的风险.

Objective To investigate the association between single nucleotide polymorphism （SNP） in the signal transducer and activator of transcription （STAT4） gene and the susceptibility of systemic lupus erythematosus （SLE） in Chinese Han population of Yunnan. Methods The Sequenom MassArray system was used to conduct the genotype in 20 SNPs of the STAT4 genes （rs10168266, rs10181656, rs11889341, rs13017460, rs1551443, rs16833249, rs2459611, rs3024879, rs3024886, rs3024894, rs3024895, rs3024933, rs3821236, rs4555370, rs6712821, rs7568275, rs7574865, rs7599504, rs8179673, rs932169） in 378 cases with SLE and 389 cases of normal control. Results Six SNPs of STAT4 gene tested here were significantly associated with SLE, particularly rs10181656 （P=5.41E-09） , and the association with SLE was significantly higher than that of European. When patients were assigned in subgroup according to the arthritis, butterfly rash, kidney damage, oral ulcers, anti-dsDNA, ANA, hematological and serositis, the G-allele frequencies of SNP rs10181656 was significant differences between SLE patients and controls （P 〈0.01）. Conclusion It suggested that polymorphism of STAT4 gene may be related to susceptibility of SLE in Chinese Hart population of Yunnan. The G-allele of rs10181656 increased the risk of SLE patients with arthritis, butterfly rash, kidney damage, oronasal ulcers, anti-dsDNA, ANA, hematological and serositis.