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Ann Hum Genet. 2017 Sep;81(5):213-223. doi: 10.1111/ahg.12203. Epub 2017 Jul 2.

Apolipoprotein E Polymorphism and Left Ventricular Failure in Beta-Thalassemia: A Multivariate Meta-Analysis.

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Department of Computer Science and Biomedical Informatics, University of Thessaly, Papasiopoulou 2-4, Lamia, 35100, Greece.


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.


ApoE; SNP; genetic association; hemoglobin; multiple outcomes; thalassemia

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