Association between a Single Nucleotide Polymorphism in the 3′-UTR of ARHGEF18 and the Risk of Nonidiopathic Pulmonary Arterial Hypertension in Chinese Population
Association between a Single Nucleotide Polymorphism in the 3′-UTR of ARHGEF18 and the Risk of Nonidiopathic Pulmonary Arterial Hypertension in Chinese Population
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DOI：
10.1155/2018/2461815
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发表时间：
2018-01-01
期刊：
影响因子：
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通讯作者：
Chen, Peng
中科院分区：
文献类型：
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作者：
Li, Ding;Sun, Yan;Chen, Peng
已发现ARHGEFI8在低氧或野百合碱(MCT)诱导的大鼠肺动脉高压模型肺组织中上调。我们使用在线SNP功能预测工具来筛选可能与ARHGEF18表达调控相关的候选SNP。结果提示，位于ARHGEFI8基因3‘端非翻译区的rs3745357可能是该过程中的一种遗传修饰。本研究旨在探讨ARHGEF18 rs3745357基因多态性与非特发性肺动脉高压易感性(NIPAH)的关系。共有293名参与者参加了病例对照研究(117名患者和176名健康对照)。采用裂解扩增多态(CAP)序列标签定位技术对rs3745357突变进行鉴定。虽然Nipah患者rs3745357的等位基因和基因型频率与对照组接近，但当我们将Nipah患者进一步划分为合并或不合并冠心病(CHD)的亚组时，发现存在显著差异。Rs3745357C等位基因频率在无冠心病史的患者中显著高于对照组(p=0.001)，而在有冠心病史的患者中显著低于对照组(p=0.017)。基因频率的分布也有很大的差异。经性别、年龄调整后，有冠心病史的患者与对照组比较差异有统计学意义。结果提示，ARHGEF18 rs3745357变异可作为Nipah遗传易感性的一个标记。
ARHGEFI8 has been identified as upregulated in the lung tissues of rat models of pulmonary artery hypertension introduced by hypoxia or monocrotaline (MCT). We used online SNP function prediction tools to screen the candidate SNPs that might be associated with the regulation of the ARHGEF18 expression. The result suggested that rs3745357 located in the 3'-untranslated region of ARHGEFI8 is probably a genetic modifier in the process. In the present study, we aimed to investigate the association between ARHGEF18 rs3745357 polymorphism and nonidiopathic pulmonary arterial hypertension susceptibility (niPAH). A total of 293 participants were included in the case-control study (117 patients and 176 healthy controls). The rs3745357 variant was discriminated by using cleaved amplification polymorphism (CAP) sequence-tagged site technology. Although the overall allele and genotype frequencies of rs3745357 in niPAH patients were close to those of the control group, significant differences have been identified when we further divided the niPAH patients into subgroups with or without coronary heart disease (CHD). Rs3745357 C allele frequency was significantly higher in niPAH patients without CHD history (p = 0.001), while the frequency was significantly lower in niPAH patients with CHD history (p = 0.017) when compared to control subjects. The distribution of genotype frequencies was also quite different. After adjustment by gender and age, significant differences were found between patients with CHD history and controls. The results suggest that the ARHGEF18 rs3745357 variant may be used as a marker for the genetic susceptibility to niPAH.