Interactive association of five candidate polymorphisms in Apelin/APJ pathway with coronary artery disease among Chinese hypertensive patients.
Interactive association of five candidate polymorphisms in Apelin/APJ pathway with coronary artery disease among Chinese hypertensive patients.
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Apelin/APJ通路五种候选多态性与中国高血压患者冠心病的交互关联
DOI：
10.1371/journal.pone.0051123
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Niu W
中科院分区：
文献类型：
--
作者：
Jin W;Su X;Xu M;Liu Y;Shi J;Lu L;Niu W
通过对apelin/angiotensin receptor-like 1（apelin/APJ）通路基因的测序，我们最近发现并验证了4个与高血压发生有关的常见多态性（rs3761581、rs 56204867、rs7119375和rs 10501367）。扩展这些发现，我们，在中国高血压患者中，试图调查这四个多态性和一个额外的有前途的候选人（rs 9943582）从这个途径与冠状动脉疾病（CAD）的风险的关联。方法/主要发现基因型来自994例散发性CAD患者和708例年龄和性别匹配的对照。所有参与者均为高血压患者，并经血管造影证实。数据用Haplo.Stats和多因素降维（MDR）软件进行统计分析。5个多态性位点的基因型分布在男女对照中均满足Hardy-Weinberg平衡。单位点分析显示，即使在控制了传统的心血管混杂因素后，冠心病患者和对照组之间检测的多态性的基因型/等位基因频率也没有显著差异（P>0.05）。在单倍型分析中，男性中对照组（1.73%）的低等位率单倍型G-A（来自apelin基因的rs 56204867和rs3761581的顺序）显著高于CAD患者（0.4%）（P = 0.047）。 进一步的相互作用分析表明，总体最佳MDR模型包括男性rs3761581（P = 0.0408）和女性rs7119375和rs 9943582（P<0.0001），这在经典逻辑回归模型中得到进一步证实。 结论我们的研究结果表明apelin基因的低外显率单倍型对男性CAD有贡献作用，更重要的是，apelin/APJ途径中遗传缺陷的相互作用可能会给中国高血压患者带来潜在风险。
Background Via sequencing the genes of apelin/angiotensin receptor-like 1 (apelin/APJ) pathway, we have recently identified and validated four common polymorphisms (rs3761581, rs56204867, rs7119375, and rs10501367) implicated in the development of hypertension. Extending these findings, we, in Chinese hypertensive patients, sought to investigate the association of these four polymorphisms and one additional promising candidate (rs9943582) from this pathway with the risk of developing coronary artery disease (CAD). Methodology/Principal Findings Genotypes were obtained from 994 sporadic CAD patients and 708 age- and sex-matched controls. All participants were hypertensives and angiographically-confirmed. Data were analyzed by Haplo.Stats and multifactor dimensionality reduction (MDR) softwares. Genotype distributions of five examined polymorphisms satisfied Hardy-Weinberg equilibrium in controls of both genders. Single-locus analyses exhibited no significant differences in the genotype/allele frequencies of examined polymorphisms between CAD patients and controls (P>0.05), even after controlling traditional cardiovascular confounders. In haplotype analyses, low-penetrance haplotype G-A (in order of rs56204867 and rs3761581 from apelin gene) was significantly overrepresented in controls (1.73%) relative to in CAD patients (0.4%) in males (P = 0.047). Further interaction analyses suggested an overall best MDR model including rs3761581 in males (P = 0.0408) and including rs7119375 and rs9943582 in females (P<0.0001), which were further substantiated in the classical logistical regression model. Conclusions Our findings demonstrated a contributive role of low-penetrance haplotype in apelin gene on CAD in males, and more importantly, interactive effects of genetic defects in apelin/APJ pathway might confer a potential risk in Chinese hypertensive patients.
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DOI：
10.1006/bbrc.1998.9489
发表时间：
1998-10-20
影响因子：
3.1
作者：
Tatemoto, K;Hosoya, M;Fujino, M
通讯作者：
Fujino, M
影响因子：
2.1
作者：
Pattin, Kristine A.;White, Bill C.;Barney, Nate;Gui, Jiang;Nelson, Heather H.;Kelsey, Karl T.;Andrew, Angeline S.;Karagas, Margaret R.;Moore, Jason H.
通讯作者：
Moore, Jason H.
DOI：
10.1056/nejmra0808700
发表时间：
2009-04-23
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hardy J;Singleton A
通讯作者：
Singleton A
影响因子：
3.4
作者：
Falcone, Colomba;Bozzini, Sara;Pelissero, Gabriele
通讯作者：
Pelissero, Gabriele
影响因子：
20.1
作者：
Kuba, Keiji;Zhang, Liyong;Penninger, Josef M.
通讯作者：
Penninger, Josef M.