Effect of apolipoprotein E polymorphism on renal transplantation.
BACKGROUND
Dyslipidemia is an important cardiovascular risk factor and is implicated in the pathogenesis of chronic graft failure in renal transplant recipients. Apolipoprotein E (apoE), a hepatic glycoprotein involved in lipid metabolism, has been associated with hypercholesterolemia and premature coronary disease.


OBJECTIVE
This study assessed the impact of apoE polymorphism on the evolution of renal transplant recipients.


METHODS
A total of 517 patients (age, 47 +/- 14 years; 62% men), who had undergone renal transplantation at least 12 months before enrollment, were assessed (mean follow-up, 5.4 +/- 2.2 years). ApoE polymorphisms (E2, E3, and E4 alleles) were analyzed using polymerase chain reaction (PCR) using genomic DNA. Donor-recipient clinical variables were assessed using univariate methods and Cox multivariate regression model.


RESULTS
Genotype frequency was as follows: E2/E2 <1%, E2/E3 10%, E3/E3 71%, E2/E4 2%, E3/E4 16%, and E4/E4 1%, with no differences between sexes. In the univariate study, E2/E4, E3/E4, and E4/E4 genotypes were related with poorer patient survival (P = .0045). In the multivariate study, the E4 allele was associated with a higher independent risk of graft loss (odds ratio [OR], 3.23; 95% confidence interval [CI], 1.44-7.21; P < .0001) and death of the patient (OR, 16.03; 95% CI, 3.28-75.18; P < .0001), but only in patients older than 60 years of age. In patients with the E4 allele, 45% of deaths were due to cardiovascular causes.


CONCLUSIONS
The genetic polymorphism of apoE (E4 allele) has an independent negative impact on patient and graft survival in the long term, particularly in older patients.
Cofán
F
F
Renal Transplant Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain. fcofan@clinic.ub.es
Cofan
M
M
Rosich
E
E
Campos
B
B
Casals
E
E
Zambon
D
D
Ros
E
E
Oppenheimer
F
F
Campistol
J M
JM
D001057:Apolipoproteins E / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics; D017931:DNA Primers; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006084:Graft Rejection / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D016030:Kidney Transplantation / Q000401:mortality / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016019:Survival Analysis; D016896:Treatment Outcome
D001057:Apolipoproteins E; D017931:DNA Primers; D004247:DNA