Investigation of 89 candidate gene variants for effects on all-cause mortality following acute coronary syndrome.
Investigation of 89 candidate gene variants for effects on all-cause mortality following acute coronary syndrome.
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DOI：
10.1186/1471-2350-9-66
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发表时间：
2008-07-12
影响因子：
--
通讯作者：
Spertus JA
中科院分区：
文献类型：
--
作者：
Morgan TM;Xiao L;Lyons P;Kassebaum B;Krumholz HM;Spertus JA
许多候选基因已被报道为急性冠状动脉综合征（ACS）的危险因素，但其对ACS后临床预后的影响尚不清楚。我们在密苏里州堪萨斯城的大学附属医院研究了811名ACS幸存者的ACS后3年死亡率与假定遗传危险因素的关系。通过系统的文献检索，我们首先确定了报告为动脉粥样硬化或ACS易感因素的遗传变异。限制我们的分析白人，以避免混杂的种族，我们基因型ACS病例的89个遗传变异的72个基因，并进行个人的Kaplan-Meier生存分析。然后，我们进行了考克斯回归，以建立多变量风险预测模型，进一步减少潜在的混淆。在检测的89种变异中，16种可能与死亡率相关（所有变异均P < 0.1），其中6种与ACS后的死亡率显著相关（P < 0.05）。虽然这些发现并不超过偶然的预期（P = 0.28），但即使在Bonferroni校正和传统心脏危险因素校正后，IRS 1 972 Arg变异相关性（P = 0.001）仍保持边缘统计学显著性（P < 0.1）。除了IRS 1可能的例外，我们得出结论，在我们的患者队列中，多个候选基因与ACS后死亡率无关。由于功效限制，P值< 0.1的16个基因变异可能需要进一步研究。我们的数据不支持这一假设，即其余73个基因与ACS后的死亡率有实质性的、临床显著的相关性。
Many candidate genes have been reported to be risk factors for acute coronary syndrome (ACS), but their impact on clinical prognosis following ACS is unknown. We examined the association of putative genetic risk factors with 3-year post-ACS mortality in 811 ACS survivors at university-affiliated hospitals in Kansas City, Missouri. Through a systematic literature search, we first identified genetic variants reported as susceptibility factors for atherosclerosis or ACS. Restricting our analysis to whites, so as to avoid confounding from racial admixture, we genotyped ACS cases for 89 genetic variants in 72 genes, and performed individual Kaplan-Meier survival analyses. We then performed Cox regression to create multivariate risk prediction models that further minimized potential confounding. Of 89 variants tested, 16 were potentially associated with mortality (P < 0.1 for all), of which 6 were significantly associated (P < 0.05) with mortality following ACS. While these findings are not more than what would be expected by chance (P = 0.28), even after Bonferroni correction and adjustment for traditional cardiac risk factors, the IRS1 972Arg variant association (P = 0.001) retained borderline statistical significance (P < 0.1). With the possible exception of IRS1, we conclude that multiple candidate genes were not associated with post-ACS mortality in our patient cohort. Because of power limitations, the 16 gene variants with P values < 0.1 may warrant further study. Our data do not support the hypothesis that the remaining 73 genes have substantial, clinically significant association with mortality after an ACS.
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DOI：
10.1016/s0197-2456(98)00037-3
发表时间：
1998-12-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
Dupont, WD;Plummer, WD
通讯作者：
Plummer, WD
影响因子：
3.5
作者：
van Dam, RM;Hoebee, B;Feskens, EJM
通讯作者：
Feskens, EJM
影响因子：
8.2
作者：
Jellema, A;Zeegers, MPA;Mensink, RP
通讯作者：
Mensink, RP
影响因子：
3.3
作者：
Schisterman EF;Whitcomb BW
通讯作者：
Whitcomb BW
影响因子：
37.8
作者：
Podgoreanu, MV;White, WD;Schwinn, DA
通讯作者：
Schwinn, DA