Dimou Niki L, Pantavou Katerina G, Bagos Pantelis G
Department of Computer Science and Biomedical Informatics, University of Thessaly, Papasiopoulou 2-4, Lamia, 35100, Greece.
Ann Hum Genet. 2017 Sep;81(5):213-223. doi: 10.1111/ahg.12203. Epub 2017 Jul 2.
Apolipoprotein E (ApoE) is potentially a genetic risk factor for the development of left ventricular failure (LVF), the main cause of death in beta-thalassemia homozygotes. In the present study, we synthesize the results of independent studies examining the effect of ApoE on LVF development in thalassemic patients through a meta-analytic approach. However, all studies report more than one outcome, as patients are classified into three groups according to the severity of the symptoms and the genetic polymorphism. Thus, a multivariate meta-analytic method that addresses simultaneously multiple exposures and multiple comparison groups was developed. Four individual studies were included in the meta-analysis involving 613 beta-thalassemic patients and 664 controls. The proposed method that takes into account the correlation of log odds ratios (log(ORs)), revealed a statistically significant overall association (P-value = 0.009), mainly attributed to the contrast of E4 versus E3 allele for patients with evidence (OR: 2.32, 95% CI: 1.19, 4.53) or patients with clinical and echocardiographic findings (OR: 3.34, 95% CI: 1.78, 6.26) of LVF. This study suggests that E4 is a genetic risk factor for LVF in beta-thalassemia major. The presented multivariate approach can be applied in several fields of research.
载脂蛋白E（ApoE）可能是导致左心室衰竭（LVF）的遗传风险因素，左心室衰竭是β地中海贫血纯合子的主要死因。在本研究中，我们通过荟萃分析方法综合了独立研究的结果，这些研究考察了ApoE对地中海贫血患者左心室衰竭发展的影响。然而，所有研究都报告了不止一个结果，因为患者根据症状严重程度和基因多态性被分为三组。因此，我们开发了一种多变量荟萃分析方法，该方法可同时处理多个暴露因素和多个比较组。荟萃分析纳入了四项个体研究，涉及613例β地中海贫血患者和664例对照。所提出的考虑对数比值比（log(ORs)）相关性的方法显示出具有统计学意义的总体关联（P值 = 0.009），这主要归因于有证据的患者（OR：2.32，95%CI：1.19，4.53）或有左心室衰竭临床和超声心动图表现的患者（OR：3.34，95%CI：1.78，6.26）中E4与E3等位基因的对比。本研究表明，E4是重型β地中海贫血患者左心室衰竭的遗传风险因素。所提出的多变量方法可应用于多个研究领域。
