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

Abstract

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.

Association of GSTT1/GSTM1 and ApoE variants with left ventricular diastolic dysfunction in thalassaemia major patients

“…There is increasing evidence which suggests us that the oxidative modification of low-density cholesterol actively participates in the sequence of events leading to cardiovascular complications [25]. Recently, Dimou et al [26] did a meta-analysis and shows E4 allele as a genetic risk factor for LVF in beta-thalassaemia major. Bazrgar et al [27] show E4 allele as a risk factor for left ventricular systolic dysfunction thalassaemia patients; however, they did not find any association with left ventricular diastolic dysfunction.…”