Apolipoprotein E epsilon4 allele as a genetic risk factor for left ventricular failure in homozygous beta-thalassemia.
In homozygous beta-thalassemia, the organ damage is mainly attributed to excessive iron deposition through the formation of oxygen free radicals. Despite appropriate transfusion and chelation therapy and low ferritin levels, patients still develop organ failure, heart failure being the main cause of death. This study was designed to determine whether the decreased antioxidant activity of the apolipoprotein E (APOE) 4 allele could represent a genetic risk factor for the development of left ventricular failure (LVF) in beta-thalassemia homozygotes. A total of 251 Greek beta-thalassemia homozygotes were studied. Patients were divided in three groups: group A (n = 151) with no cardiac impairment, group C (n = 47) with LVF, and 53 patients with LV dilatation and normal LV systolic function constituted the group B. DNA was obtained from all patients, and the polymerase chain reaction was used to analyze the polymorphism at the APOE locus. The APOE allele frequencies were compared with those of a Greek control sample of 216 healthy blood donors. Patients with no cardiac impairment had an APOE 4 allele frequency (7.9%) not different from population controls (6.5%, P > .05), while patients with LVF had a significantly higher frequency of APOE 4 (12.8%) than the controls (P < .05, odds ratio = 2.11, 95% confidence interval 1.03 to 4.32). The APOE 4 allele may represent an important genetic risk factor for the development of organ damage in homozygous beta-thalassemia.
Economou-Petersen
E
E
Hellenic Red Cross Hospital, Athens; the Eginition University Hospital, Athens.
Aessopos
A
A
Kladi
A
A
Flevari
P
P
Karabatsos
F
F
Fragodimitri
C
C
Nicolaidis
P
P
Vrettou
H
H
Vassilopoulos
D
D
Karagiorga-Lagana
M
M
Kremastinos
D T
DT
Petersen
M B
MB
D000293:Adolescent; D000328:Adult; D000483:Alleles; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001803:Blood Transfusion; D015913:Chelation Therapy; D002648:Child; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006115:Greece / Q000453:epidemiology; D006333:Heart Failure / Q000453:epidemiology / Q000209:etiology*; D006720:Homozygote; D006801:Humans; D007501:Iron; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species; D012307:Risk Factors; D012720:Severity of Illness Index; D018487:Ventricular Dysfunction, Left / Q000453:epidemiology / Q000209:etiology*; D017086:beta-Thalassemia / Q000150:complications* / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics / Q000628:therapy
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D017382:Reactive Oxygen Species; D007501:Iron