Zhang Yue-Miao, Zhou Xu-Jie, Cheng Fa-Juan, Qi Yuan-Yuan, Hou Ping, Zhao Ming-Hui, Zhang Hong
Renal Division, Peking University First Hospital, Beijing 100034, China; Peking University Institute of Nephrology, Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing 100034, China.
J Immunol Res. 2016;2016:1343760. doi: 10.1155/2016/1343760. Epub 2016 Jun 28.
Objectives. The variant rs3828903 within MICB, a nonclassical MHC class I chain-related gene, was detected to contribute to systemic lupus erythematosus (SLE) in a Caucasian population. This study aimed to investigate the association in a northern Han Chinese population. Methods. We recruited 1077 SLE patients and 793 controls for analysis. rs3828903 was genotyped by TaqMan allele discrimination assay. Using the public databases, its functional annotations and gene differential expression analysis of MICB were evaluated. Results. Significant association between the allele G of rs3828903 and risk susceptibility to SLE was observed after adjusting for sex and age (P = 1.87 × 10(-2)). In silico analyses predicted a higher affinity to transcription factors for allele G (risk) and cis-expression quantitative trait loci (cis-eQTL) effects of rs3828903 in multiple tissues (P ranging from 2.79 × 10(-6) to 6.27 × 10(-38)). Furthermore, higher mRNA expressions of MICB were observed in B cells, monocytes, and renal biopsies from SLE patients compared to controls. Conclusion. An association between rs3828903 and susceptibility to SLE has been detected in a Chinese population. This together with the functional annotations of rs3828903 converts MICB into a main candidate in the pathogenesis of SLE.
目的。在高加索人群中检测到非经典MHC I类链相关基因MICB内的rs3828903变异与系统性红斑狼疮（SLE）有关。本研究旨在调查中国北方汉族人群中的这种关联。方法。我们招募了1077例SLE患者和793名对照进行分析。通过TaqMan等位基因鉴别分析对rs3828903进行基因分型。利用公共数据库，评估其功能注释以及MICB的基因差异表达分析。结果。在调整性别和年龄后，观察到rs3828903的等位基因G与SLE风险易感性之间存在显著关联（P = 1.87×10⁻²）。计算机分析预测等位基因G（风险）对转录因子具有更高的亲和力，并且rs3828903在多个组织中具有顺式表达数量性状位点（cis - eQTL）效应（P范围为2.79×10⁻⁶至6.27×10⁻³⁸）。此外，与对照相比，在SLE患者的B细胞、单核细胞和肾活检组织中观察到MICB的mRNA表达更高。结论。在中国人群中检测到rs3828903与SLE易感性之间存在关联。这与rs3828903的功能注释一起使MICB成为SLE发病机制中的主要候选基因。
