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Effect of apolipoprotein E and C-III polymorphisms on lipid profile and cardiovascular risk in renal transplant recipients
Effect of Apolipoprotein E and C-III Polymorphisms on Lipid Profile and Cardiovascular Risk in Renal Transplant Recipients E. Rodrigo, D. Gonza´lez-Lamun˜o, D. Isla, G. Ferna´ndez-Fresnedo, J. C. Ruiz, C. Pin˜era, I. Herra´ez, M. Arias
C
ARDIOVASCULAR disease (CVD) is the main cause of morbidity and mortality in renal transplant recipients.1 Several risk factors for CVD, such as lipid abnormalities and insulin resistance, may partly explain the accelerated development of atherosclerosis following renal transplantation.1 Polymorphisms of the apolipoprotein (apo) E and C-III genes modulate the lipid and carbohydrate metabolism.2,3 The apo E4 allele has been reported to be associated with hyperlipidemia and a high prevalence of atherosclerosis in general population.2 The S2 allele of the Sstl polymorphism of the apo C-III gene has been associated with hypertriglyceridemia, high blood pressure, and increased risk of coronary artery disease,3 all of which are characteristics of the transplant-related insulin-resistant state. However, little is known about the influence of apo E and C-III polymorphisms on dyslipidemia in renal transplant recipients. Whether apo E and C-III polymorphisms has an influence on the prevalence of atherosclerosis in renal transplant recipients remains to be clarified. MATERIALS AND METHODS Clinical assessment, biochemical analyses, genotyping for apo C-III, and apo E polymorphisms were performed on 110 consecutively examined patients undergoing kidney transplantation in Valdecilla Hospital. Demographic data were obtained for each subject from the clinical chart histories, selecting risk factors for CVD. Data about cardiovascular diseases were collected. Genomic DNA was isolated from whole blood anticoagulated with EDTA.4 Apo E polymorphisms were determined by means of polymerase chain reaction (PCR), specific digestion with Hhal (Promega), and electrophoresis in 12% acrylamida gel. Primers used for amplification were 5⬘ TAA GCT TGG CAC GGC TGT CCA AGG A 3⬘ and 5⬘ ACA GAA TTC GCC CCG GCC TGG TAC AC 3⬘. Genotype characterization of the apo C-III gene was performed by PCR, allele-specific digestion of the amplified products with the restriction enzyme Sstl (Promega), and electrophoresis in 2% agarose gel. Primers used for amplification were 5⬘ CAG AAG GTG GAT AGA GCG 3⬘ and 5⬘ TGA CCG ATG GCT TCA GTT 3⬘.
RESULTS
Serum levels of cholesterol and triglycerides did not differ significantly among patients with different alleles. The
0041-1345/01/$–see front matter PII S0041-1345(01)02585-4 3676
distribution of the three apo E alleles (E2 3.6%, E3 88.6%, E4 7.7%) and the S2 (6.3%) allele of apo C-III gene was similar to general population.3,5 There were no significant differences in the prevalence of hypertension, cerebrovascular disease, peripheral vascular disease, global atherosclerosis, diabetes mellitus, and death among patient groups with apo E and C-III polymorphisms. The odds ratio for ischemic heart disease among the patients with E4 allele was 4.07 (95% confidence interval, 1.08 to 15.29) CONCLUSIONS
The apo E and C-III allele frequencies in our group of renal transplant recipients is similar to general population.3,5 Previous reports have shown that in the general population, the apo E4 allele and the apo C-III S2 allele have an association with dyslipemia and atherosclerosis.2,3 In our group of renal transplant recipients, these polymorphisms appear to have little association with the prevalence of cardiovascular complications and hyperlipidemia. Only the presence of E4 allele was a risk factor for coronary artery disease. Other factors can influence more than these polymorphisms on the development of CVD and dyslipidemia in renal transplant. REFERENCES 1. Kasiske BL, Guijarro C, Massy ZA, et al: J Am Soc Nephrol 7:158, 1996 2. Wilson PW, Myers RH, Larson MG, et al: JAMA 272:1666, 1994 3. Salas J, Jansen S, Lopez-Miranda J, et al: Am J Clin Nutr 68:396, 1998 4. Miller SA, Dykes DD, Polesky HF: Nucleic Acids Res 16: 1215, 1988. 5. Imura T, Kimura H, Gejyo F: Kidney Int 56(suppl 71):245, 1999
From the Departments of Nephrology and Pediatry, Hospital Valdecilla, Santander, Spain. Address reprint request to Dr E. Rodrigo, Department of Nephrology, Hospital Valdecilla, Avda, Valdecilla s/n 39008, Santander, Spain.
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 33, 3676 (2001)
C
ARDIOVASCULAR disease (CVD) is the main cause of morbidity and mortality in renal transplant recipients.1 Several risk factors for CVD, such as lipid abnormalities and insulin resistance, may partly explain the accelerated development of atherosclerosis following renal transplantation.1 Polymorphisms of the apolipoprotein (apo) E and C-III genes modulate the lipid and carbohydrate metabolism.2,3 The apo E4 allele has been reported to be associated with hyperlipidemia and a high prevalence of atherosclerosis in general population.2 The S2 allele of the Sstl polymorphism of the apo C-III gene has been associated with hypertriglyceridemia, high blood pressure, and increased risk of coronary artery disease,3 all of which are characteristics of the transplant-related insulin-resistant state. However, little is known about the influence of apo E and C-III polymorphisms on dyslipidemia in renal transplant recipients. Whether apo E and C-III polymorphisms has an influence on the prevalence of atherosclerosis in renal transplant recipients remains to be clarified. MATERIALS AND METHODS Clinical assessment, biochemical analyses, genotyping for apo C-III, and apo E polymorphisms were performed on 110 consecutively examined patients undergoing kidney transplantation in Valdecilla Hospital. Demographic data were obtained for each subject from the clinical chart histories, selecting risk factors for CVD. Data about cardiovascular diseases were collected. Genomic DNA was isolated from whole blood anticoagulated with EDTA.4 Apo E polymorphisms were determined by means of polymerase chain reaction (PCR), specific digestion with Hhal (Promega), and electrophoresis in 12% acrylamida gel. Primers used for amplification were 5⬘ TAA GCT TGG CAC GGC TGT CCA AGG A 3⬘ and 5⬘ ACA GAA TTC GCC CCG GCC TGG TAC AC 3⬘. Genotype characterization of the apo C-III gene was performed by PCR, allele-specific digestion of the amplified products with the restriction enzyme Sstl (Promega), and electrophoresis in 2% agarose gel. Primers used for amplification were 5⬘ CAG AAG GTG GAT AGA GCG 3⬘ and 5⬘ TGA CCG ATG GCT TCA GTT 3⬘.
RESULTS
Serum levels of cholesterol and triglycerides did not differ significantly among patients with different alleles. The
0041-1345/01/$–see front matter PII S0041-1345(01)02585-4 3676
distribution of the three apo E alleles (E2 3.6%, E3 88.6%, E4 7.7%) and the S2 (6.3%) allele of apo C-III gene was similar to general population.3,5 There were no significant differences in the prevalence of hypertension, cerebrovascular disease, peripheral vascular disease, global atherosclerosis, diabetes mellitus, and death among patient groups with apo E and C-III polymorphisms. The odds ratio for ischemic heart disease among the patients with E4 allele was 4.07 (95% confidence interval, 1.08 to 15.29) CONCLUSIONS
The apo E and C-III allele frequencies in our group of renal transplant recipients is similar to general population.3,5 Previous reports have shown that in the general population, the apo E4 allele and the apo C-III S2 allele have an association with dyslipemia and atherosclerosis.2,3 In our group of renal transplant recipients, these polymorphisms appear to have little association with the prevalence of cardiovascular complications and hyperlipidemia. Only the presence of E4 allele was a risk factor for coronary artery disease. Other factors can influence more than these polymorphisms on the development of CVD and dyslipidemia in renal transplant. REFERENCES 1. Kasiske BL, Guijarro C, Massy ZA, et al: J Am Soc Nephrol 7:158, 1996 2. Wilson PW, Myers RH, Larson MG, et al: JAMA 272:1666, 1994 3. Salas J, Jansen S, Lopez-Miranda J, et al: Am J Clin Nutr 68:396, 1998 4. Miller SA, Dykes DD, Polesky HF: Nucleic Acids Res 16: 1215, 1988. 5. Imura T, Kimura H, Gejyo F: Kidney Int 56(suppl 71):245, 1999
From the Departments of Nephrology and Pediatry, Hospital Valdecilla, Santander, Spain. Address reprint request to Dr E. Rodrigo, Department of Nephrology, Hospital Valdecilla, Avda, Valdecilla s/n 39008, Santander, Spain.
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 33, 3676 (2001)