糖皮质激素受体基因多态性与中国人群系统性红斑狼疮的关联。
Association of glucocorticoid receptor gene polymorphisms with systemic lupus erythematosus in a Chinese population.
机构信息
Department of Rheumatology and Immunology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
出版信息
Int J Rheum Dis. 2017 Dec;20(12):2053-2061. doi: 10.1111/1756-185X.13191. Epub 2017 Oct 6.
OBJECTIVES
To identify the association of glucocorticoid receptor (GR) gene polymorphism with systemic lupus erythematosus (SLE).
METHODS
A case-control study was carried out, in which 400 Chinese patients with SLE and 400 normal people were enrolled. DNA was extracted using a genomic DNA extraction kit, and tagged single nucleotide polymorphisms (SNPs) were identified by Haploview (4.0) Project from the Chinese HapMap Project. Eighteen tagged SNPs of the GR gene were genotyped by the Multiplex SNaPshot technique.
RESULTS
Two GR gene SNPs were associated with the pathogenesis of SLE: rs6865292 (dominant model: crude odds ratio [OR] = 1.526, 95% CI: 1.151-2.025, P = 0.003; adjusted OR = 1.525, 95% CI: 1.149-2.023, P = 0.004; P = 0.036) and rs9324921 (dominant model: crude OR = 1.556, 95% CI: 1.173-2.062, P = 0.002; adjusted OR = 1.553, 95% CI: 1.171-2.060, P = 0.002; P = 0.036). The haplotype analysis of GR gene SNPs manifested that the haplotype of 'CCGGG' (OR = 2.701, 95% CI: 1.348-5.410, P = 0.004; P = 0.036) was a risk factor for the development of SLE. A lower frequency of A-allele of SNP rs4607376 (P = 0.021; OR = 0.794, 95% CI: 0.652-0.966, P = 0.126), higher frequency of C-allele of SNP rs6865292 (P = 0.019, OR = 1.317, P = 0.126) and A-allele of SNP rs9324921 (P = 0.019, OR = 1.317, P = 0.126) may be risk factors for developing SLE. The rs7719514 (recessive model: crude P = 0.044; adjusted P = 0.044, P = 0.264), rs7701443 (recessive model: crude P = 0.044, adjusted P = 0.045; P = 0.264), rs4607376 (recessive model: crude P = 0.027; adjusted P = 0.026; P = 0.264) and haplotype 'CAGCG' (P = 0.044; P = 0.198) showed marginal association with the pathogenesis of SLE. In the case group, there were no significant differences between non-lupus nephritis and lupus nephritis. Further, we found that the SNP rs12054797 (F = 3.228, P = 0.041, P = 0.342), rs2963156 (F = 3.163, P = 0.043, P = 0.342) might be marginally associated with disease activity.
CONCLUSIONS
The study indicates that GR genetic polymorphisms may play a major role in the pathogenesis and development of SLE.
目的
鉴定糖皮质激素受体（GR）基因多态性与系统性红斑狼疮（SLE）之间的关联。
方法
开展病例对照研究，纳入 400 例中国 SLE 患者和 400 例正常人。采用基因组 DNA 提取试剂盒提取 DNA，采用中国 HapMap 项目的 Haploview（4.0）项目鉴定标签单核苷酸多态性（SNP）。采用多重 SNaPshot 技术对 GR 基因的 18 个标签 SNP 进行基因分型。
结果
有两个 GR 基因 SNP 与 SLE 的发病机制相关：rs6865292（显性模型：粗比值比[OR] = 1.526，95%可信区间[CI]：1.151-2.025，P = 0.003；调整 OR = 1.525，95% CI：1.149-2.023，P = 0.004；P = 0.036）和 rs9324921（显性模型：粗 OR = 1.556，95% CI：1.173-2.062，P = 0.002；调整 OR = 1.553，95% CI：1.171-2.060，P = 0.002；P = 0.036）。GR 基因 SNP 的单倍型分析显示，GR 基因 SNP 的“CCGGG”单倍型（OR = 2.701，95% CI：1.348-5.410，P = 0.004；P = 0.036）是 SLE 发病的危险因素。SNP rs4607376 的 A 等位基因（P = 0.021；OR = 0.794，95% CI：0.652-0.966，P = 0.126）的频率较低，SNP rs6865292 的 C 等位基因（P = 0.019，OR = 1.317，P = 0.126）和 SNP rs9324921 的 A 等位基因（P = 0.019，OR = 1.317，P = 0.126）的频率较高，可能是 SLE 发病的危险因素。SNP rs7719514（隐性模型：粗 P = 0.044；调整 P = 0.044，P = 0.264）、rs7701443（隐性模型：粗 P = 0.044，调整 P = 0.045；P = 0.264）、rs4607376（隐性模型：粗 P = 0.027；调整 P = 0.026；P = 0.264）和单倍型“CAGCG”（P = 0.044；P = 0.198）与 SLE 的发病机制存在边缘关联。在病例组中，狼疮肾炎与非狼疮肾炎之间无显著差异。进一步发现，SNP rs12054797（F = 3.228，P = 0.041，P = 0.342）、rs2963156（F = 3.163，P = 0.043，P = 0.342）可能与疾病活动度有边缘关联。
结论
该研究表明，GR 基因多态性可能在 SLE 的发病机制和发展中起主要作用。
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