Genome-wide association study identifies loci and candidate genes for non-idiopathic pulmonary hypertension in Eastern Chinese Han population.
Genome-wide association study identifies loci and candidate genes for non-idiopathic pulmonary hypertension in Eastern Chinese Han population.
复制标题
全基因组关联研究确定了中国东部汉族人群非特发性肺动脉高压的位点和候选基因
DOI：
10.1186/s12890-018-0719-0
复制
发表时间：
2018-10-05
影响因子：
3.1
通讯作者：
Chen F
中科院分区：
文献类型：
--
作者：
Yin C;Li K;Yu Y;Huang H;Yu Y;Wang Z;Yan J;Pu Y;Li Z;Li D;Chen P;Chen F
肺动脉高压（PH）是一种罕见疾病，其特征是肺小动脉增殖和闭塞，与高死亡率相关。 PH 的发病机制很复杂且尚未完全了解，其中包括改变血管结构和功能的遗传和环境因素。因此，我们旨在通过针对 14 个候选基因的 143 个标签 SNP 来揭示 PH 的潜在遗传病因。本研究共纳入 208 名中国汉族人群，其中包括 109 名非特发性 PH 患者和 99 名健康对照者。数据显示，Bonferroni 校正后，2 个 SNP 与 PH 总体易感性相关，p< 3×10− 4。排名最高的是位于 6 号染色体 Nox3 基因内的 rs6557421 (p = 4.5×10− 9)。位于 Tbx4 基因中的另一个 SNP rs3744439 也显示出与 PH 敏感性相关的证据 (p = 1.2×10− 6)。 rs6557421和rs3744439的基因型频率分布在PH患者和对照之间存在显着差异。在共显性或隐性模型中，与 GG 或 GG/GT 携带者相比，具有 rs6557421 TT 基因型的个体患 PH 的风险分别增加 10.72 倍/14.20 倍（TT 与 GG：95%CI = 4.79–24.00；TT 与 GG/GT： 95%CI = 6.65–30.33）。至于 rs3744439，AG 基因型仅出现在健康对照中，但尚未在 PH 患者中观察到。我们通过使用来自全球五个地区的 26 个不同人群进一步验证了结果，包括非洲 (AFR)、美洲 (AMR)、东亚 (EAS)、欧洲 (EUR) 和南亚 (SAS)。与目前的病例对照研究结果一致，观察到的 SNP 基因型频率在世界各地的 PH 患者和健康个体之间存在显着不同。结果表明，Nox3 中的 rs6557421 变异和 Tbx4 中的 rs3744439 变异可能对个体对肺动脉高压的易感性产生潜在影响，从而可能导致肺动脉高压的治疗或诊断方法。
Pulmonary hypertension (PH) is a rare disease characterized by proliferation and occlusion of small pulmonary arterioles, which has been associated with a high mortality rate. The pathogenesis of PH is complex and incompletely understood, which includes both genetic and environmental factors that alter vascular structure and function. Thus we aimed to reveal the potential genetic etiology of PH by targeting 143 tag SNPs of 14 candidate genes. Totally 208 individuals from Chinese Han population were enrolled in the present study, including 109 non-idiopathic PH patients and 99 healthy controls. The data revealed that 2 SNPs were associated with PH overall susceptibility at p < 3×10− 4 after Bonferroni correction. The top hit was rs6557421 (p = 4.5×10− 9), located within Nox3 gene on chromosome 6. Another SNP rs3744439 located in Tbx4 gene, also showed evidence of association with PH susceptibility (p = 1.2×10− 6). The distribution of genotype frequencies of rs6557421 and rs3744439 have dramatic differences between PH patients and controls. Individuals with rs6557421 TT genotype had a 10.72-fold/14.20-fold increased risk to develop PH when compared with GG or GG/GT carriers in codominant or recessive model, respectively (TT versus GG: 95%CI = 4.79–24.00; TT versus GG/GT: 95%CI = 6.65–30.33). As for rs3744439, AG genotype only occurred in healthy controls but has not been observed in PH patients. We further validated the result by using 26 different populations from five regions around the globe, including African (AFR), American (AMR), East Asian (EAS), European (EUR), and South Asian (SAS). In consistent with the present case-control study’s results, significantly different genotype frequencies of the observed SNPs existed between PH patients and healthy individuals from all over the world. The results suggested that rs6557421 variant in Nox3 and rs3744439 variant in Tbx4 might have potential effect on individual susceptibility to pulmonary hypertension, which could lead to therapeutic or diagnosis approaches in PH.
登录
查看更多内容
影响因子：
15.9
作者：
Xie, Ting;Liang, Jiurong;Noble, Paul W.
通讯作者：
Noble, Paul W.
影响因子：
5.8
作者：
Sole, Xavier;Guino, Elisabet;Moreno, Vitor
通讯作者：
Moreno, Vitor
影响因子：
15.9
作者：
Zhang, Xuchen;Shan, Peiying;Lee, Patty J.
通讯作者：
Lee, Patty J.
影响因子：
3.7
作者：
Yang H;Zhang W;Pan H;Feldser HG;Lainez E;Miller C;Leung S;Zhong Z;Zhao H;Sweitzer S;Considine T;Riera T;Suri V;White B;Ellis JL;Vlasuk GP;Loh C
通讯作者：
Loh C
DOI：
10.1161/circgen.117.001887
发表时间：
2018-04
期刊：
Circulation. Genomic and precision medicine
影响因子：
--
作者：
Zhu N;Gonzaga-Jauregui C;Welch CL;Ma L;Qi H;King AK;Krishnan U;Rosenzweig EB;Ivy DD;Austin ED;Hamid R;Nichols WC;Pauciulo MW;Lutz KA;Sawle A;Reid JG;Overton JD;Baras A;Dewey F;Shen Y;Chung WK
通讯作者：
Chung WK