Apolipoprotein E gene polymorphism in renal transplant recipients: effects on lipid metabolism, atherosclerosis and allograft function.
BACKGROUND
Atherosclerosis is a serious complication and leading cause of mortality in renal transplant recipients (RTRs). Hyperlipidemia may be associated with progression of renal disease and chronic allograft dysfunction. Similarities in the pathogenesis of glomerulosclerosis and atherosclerosis have been proposed. Apolipoprotein (apo) E gene code forms three major isoforms (E2, E3, and E4) with variable effects on lipid metabolism.


METHODS
A total of 118 patients, at a mean age of 40 +/- 8 yr, were included in the study. Apo E genotyping was carried out on genomic DNA using polymerase chain reaction and restriction enzyme. Carotid artery intima media thickness and atherosclerotic plaques were evaluated by B-mode ultrasonography. The plasma levels of lipids and lipoproteins and acute phase reactants were also studied. Allograft function was evaluated by measuring serum creatinine and creatinine clearance values.


RESULTS
The frequencies of E2, E3, and E4 alleles were 0.10, 0.78, and 0.12 respectively. Carotid artery atherosclerosis was found in 25% of E2 carriers, 30% of E3 carriers, and 57% of E4 carriers. Total cholesterol, total triglyceride, low-density lipoprotein, very low-density lipoprotein, apo B 100 levels were found to be higher in apo E4 carriers. Median apo A1 level was higher and allograft functions were better in apo E2 carriers (p < 0.05). Multiple regression analysis showed that allograft functions were negatively correlated with elevated acute phase reactants (p < 0.01) and only the age, but not the apo E genotypes, was an independent risk factor for atherosclerotic vascular disease (p < 0.01).


CONCLUSIONS
The pathogenetic events linking lipid metabolism and allograft functions and development of atherosclerosis are complex and multifactorial in RTRs. Our results showed that apo E genotypes have influences on lipids, lipoproteins and allograft functions. The ultimate role of apo E4 gene polymorphism as a risk factor for development and progression of atherosclerosis in RTRs should be sought in further studies.
Kahraman
Serkan
S
Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey. marici@hacettepe.edu.tr
Kiykim
Ahmet Alper
AA
Altun
Bülent
B
Gençtoy
Gültekin
G
Arici
Mustafa
M
Gulsun
Meltem
M
Erdem
Yunus
Y
Yasavul
Unal
U
Turgan
Cetin
C
Cağlar
Sali
S
D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D001161:Arteriosclerosis / Q000235:genetics*; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology*; D050356:Lipid Metabolism; D008055:Lipids / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D014184:Transplantation, Homologous
D001057:Apolipoproteins E; D008055:Lipids