2019 年第 1 期 第 14 卷

循环可溶性ST2浓度相关基因多态性与主动脉瘤的关系

Relation between circulating soluble ST2 concentration related gene polymorphism and aortic aneurysm

作者：王媛姜文溪王雪王绿娅柯兵兵杜杰

英文作者：

单位：100029首都医科大学附属北京安贞医院北京市心肺血管疾病研究所心血管生物研究室

英文单位：

关键词：主动脉瘤；ST2；单核苷酸多态性

英文关键词：

• 摘要：

• 【摘要】目的    探讨中国人群循环可溶性ST2浓度相关基因多态性与主动脉瘤的关系。方法    选择2014年1月至2016年12月首都医科大学附属北京安贞医院收治的主动脉瘤患者331例（观察组），通过已发表的ST2浓度相关基因的文献纳入有重要意义的27个单核苷酸多态性（SNP），提取观察组患者全基因组DNA，聚合酶链反应扩增后，采用基质辅助激光解吸电离飞行时间质谱仪分析，检测结果使用TYPER 4.0软件获取原始数据及基因分型图。选择国际千人基因组计划中的208名中国人基因信息为对照组。对2组研究对象基因型进行分析，比较2组研究对象等位基因分布情况，对差异最显著基因的等位基因频率与主动脉瘤发病的关系进行Logistic回归分析。结果    在27个SNP中，6个SNP不满足次要等位基因频率>0.01，分别为rs12987900、rs12997225、rs13015695、rs11693697、rs13029918、rs11465699，不纳入后续分析。其余21个SNP经检验均符合哈迪-温伯格平衡（均P>0.001）。2组研究对象rs1420103、rs17027037、rs17027230、rs12463588基因型分布比较差异均有统计学意义（均P<0.05），其中位于ST2基因上的rs1420103基因型分布在2组间差异最显著。观察组共329例患者检出rs1420103基因型，其中A等位基因检出频次为346（52.6%），C等位基因检出频次为312（47.4%）；对照组A和C等位基因检出频次分别为183（44.0%）和233（56.0%）。观察组rs14020103的A等位基因频率高于对照组，rs1420103与主动脉瘤的发生显著相关（比值比=1.402，95%置信区间：1.096~1.793，P=0.007）。结论    rs1420103的A等位基因是主动脉瘤的危险因素。

• 【Abstract】Objective    To investigate the relation between circulating soluble ST2 concentration related gene polymorphism and aortic aneurysm. Methods    A total of 331 patients with aortic aneurysm admitted to Beijing Anzhen Hospital, Capital Medical University from January 2014 to December 2016 were selected as observation group. Twenty-seven significant single nucleotide polymorphisms（SNPs） of ST2 concentration related genes reported in published literatures were detected. Detection process included whole genomic DNA extraction, polymerase chain reaction amplification, matrix-assisted laser desorption ionization time-of-flight mass spectrometry and genotyping analysis by TYPER 4.0 software. Genetic information of 208 Chinese people in the 1 000 Genomes Project were control group. Genotypes and allele distributions were analyzed between groups. Relation between allele frequencies of certain genes and risk of aortic aneurysm was analyzed by Logistic regression. Results    Minor allele frequencies of 6 SNPs(rs12987900, rs12997225, rs13015695, rs11693697, rs13029918 and rs11465699) were less than 0.01 and they were excluded. Remaining 21 SNPs were tested to met the Hardy-Weinberg equilibrium(all P>0.001). There were significant differences of rs1420103, rs17027037, rs17027230 and rs12463588 genotype distribution between groups(P<0.05). Distribution of rs1420103 showed the most significant difference between groups. Genotype rs1420103 was detected in 329 patients in the observation group; frequencies of A and C alleles were 346(52.6%) and 312(47.4%). Frequencies of A and C alleles were 183(44.0%) and 233(56.0%) in the control group. Frequency of rs14020103 A allele in the observation group was higher than that in the control group; rs1420103 genotype was correlated with aortic aneurysm(odds ratio=1.402, 95% confidence interval: 1.096-1.793, P=0.007). Conclusion    Allele A of rs1420103 gene is a risk factor of aortic aneurysm.