线粒体DNA D-loop区单核苷酸多态性与类风湿关节炎发病年龄的关系研究

背景　类风湿关节炎（RA）为临床常见疾病，其发病原因尚不明确。既往研究显示，40~60岁为RA的高发年龄，线粒体DNA（mtDNA）D-loop区的单核苷酸多态性（SNP）对肿瘤、肾病等多种疾病的发病年龄具有预测价值，但是，其与RA患者发病年龄的关系尚未见报道。目的　探讨mtDNA D-loop区SNP与RA发病年龄的关系。方法　选取2017年5—12月于河北医科大学第二医院风湿免疫科住院的85例RA患者为研究对象，提取RA患者外周血中mtDNA，通过PCR扩增和基因循环测序，分析mtDNA D-loop区的SNP位点。采用Kaplan-Meier法绘制RA患者发病年龄生存曲线，并采用Log-rank法进行检验；采用Cox比例风险模型分析发病年龄的风险因素。结果　Log-rank检验结果显示，mtDNA D-loop区SNP位点16519，携带低频率等位基因T基因型的患者发病年龄早于携带高频率等位基因C基因型的患者（χ2=5.395，P=0.020）。Cox比例风险模型结果显示，mtDNA D-loop区SNP位点16519是RA发病年龄的独立预测因子〔HR=1.750，95%CI（1.047，2.925），P=0.033〕。结论　RA的发病年龄可能与mtDNA D-loop区SNP有关，对于mtDNA D-loop区SNP序列的分析有助于早期识别发生RA的高风险患者。

Single-nucleotide Polymorphism of Mitochondrial DNA Displacement Loop and Age-at-onset of Rheumatoid Arthritis

Background Rheumatoid arthritis(RA)is a common clinical disease,the cause of which remains unknown.Previous studies have shown that 40 to 60 years old is the high incidence age of RA.The single-nucleotide polymorphisms(SNPs)of mitochondrial DNA(mtDNA)displacement loop(D-loop)have been shown to have predictive value for the ageat-onset of various diseases including tumor and kidney disease,but its relationship with the age-at-onset of RA patients has not been reported.Objective To explore the relationship of SNPs in the mtDNA D-loop with the age-at-onset of RA.Methods 85 patients with RA who were hospitalized in the Department of Rheumatology and Immunology,the Second Hospital of Hebei Medical University from May to December 2017 were selected.PCR amplification and sequence analysis were used to analyze the SNPs in the D-loop of mtDNA in peripheral blood.The survival curves associated with age-at-onset were drawn by Kaplan-Meier method,and were compared by the Log-rank test.And the Cox proportional hazards model was used to analyze the risk factors of age-at-onset.Results Log-rank test results showed that the age-at-onset of patients with minor allele T genotype was earlier than that of those with major allele C genotype(χ^2=5.395,P=0.020)in the nucleotide 16519 of mtDNA D-loop.The results of the Cox proportional hazards model showed that the nucleotide 16519 in the mtDNA D-loop was an independent predictor of ageat-onset of RA〔HR=1.750,95%CI(1.047,2.925),P=0.033〕.Conclusion The age-at-onset of RA may be related to the SNP in the mtDNA D-loop.Analysis of the SNP in the mtDNA D-loop can help identify high-risk patients with early-onset of RA.