TNIP1基因多态性与汉族人系统性红斑狼疮相关性研究

Association analysis between TNIP1 gene polymorphisms and systemic lupus erythematosus in a Chinese Han population

目的：探讨人肿瘤坏死因子α诱导蛋白3（TNFAIP3）相互作用蛋白1（TNIP1）基因多态性与汉族人系统性红斑狼疮（SLE）的遗传关联性。方法收集284例汉族人 SLE 和630例汉族人对照，选择 TNIP1基因区域120个单核苷酸多态性（SNP），利用连接酶检测反应（LDR）对其进行基因分型，对分型数据利用 PLINK 1.07和 Haploview 软件进行统计分析。结果经过数据质控，最终105个 SNP 的分型数据进入最终统计分析。rs3805433 C、rs12516176 C、rs6869605 C 和 rs4958882 G 的等位基因频率在 SLE 组（参考等位基因频率0.301～0.306）高于对照组（参考等位基因频率0.221～0.225），差异有统计学意义（OR：1.50～1.53，均 P 〈4.72×10^-4）。这4个SNP 间存在强连锁不平衡（r2≥0.871，D′≥0.938），且与既往报道的 SLE 相关 SNP rs10036748间存在中等程度的连锁不平衡（r^2≥0.073，D′≥0.868）。单倍型分析发现，单倍型（H2：CCCGT）在病例组中的频率（0.290）显著高于对照组（0.210），差异有统计学意义（OR =1.54，P 〈4.72×10^-4）。结论 TNIP1基因多态性与汉族人 SLE具有相关性。

Objective To investigate association between polymorphisms of the tumor necrosis factor α-induced protein 3 （TNFAIP3）interacting protein 1 （TNIP1）gene and systemic lupus erythematosus （SLE）in a Chinese Han population. Methods Blood samples were collected from 284 patients with SLE of Han nationality（SLE group）and 630 healthy controls of Han nationality （control group）. Ligase detection reaction （LDR）was performed to determine the genotypes of 120 single nucleotide polymorphisms （SNPs）in the TNIP1 gene. Data were analyzed with the PLINK 1.07 package and Haploview software. Results After quality control, data on 105 SNPs underwent statistical analysis finally. Four SNPs including rs3805433, rs12516176, rs6869605 and rs4958882 in the TNIP1 gene were significantly associated with SLE （OR： 1.50 - 1.53, all P 〈 4.72 ×10^-4）, and there was a significant increase in the frequency of rs3805433 C, rs12516176 C, rs6869605 C and rs4958882 G alleles in the SLE group （0.301 - 0.306）compared with the control group （0.221 - 0.225）. There was strong linkage disequilibrium between these 4 SNPs （r2 ≥ 0.871, D′ ≥ 0.938）. In addition, moderate linkage disequilibrium was observed between these 4 SNPs and a previously reported SLE-related SNP rs10036748 （r^2 ≥ 0.073, D′ ≥ 0.868）. The frequency of the haplotype H2： CCCGT was significantly higher in the SLE group than in the control group（0.290 vs. 0.210, OR = 1.54, P 〈 4.72 ×10^-4）. Conclusion TNIP1 gene polymorphisms are associated with SLE in Chinese Han population.