Genetic variants in genes related to lipid metabolism and atherosclerosis, dyslipidemia and atorvastatin response

Author(s):Show less -

Rodrigues, A. C. ^[1] ; Sobrino, B. ^[2] ; Genvigir, F. D. V. ^[1] ; Willrich, M. A. V. ^[1] ; Arazi, S. S. ^[1] ; Dorea, E. L. ^[3] ; Bernik, M. M. S. ^[3] ; Bertolami, M. ^[4] ; Faludi, A. A. ^[4] ; Brion, M. J. ^{[2, 5]} ; Carracedo, A. ^[2] ; Hirata, M. H. ^[1] ; Hirata, R. D. C. ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut, BR-09500900 Sao Paulo - Brazil

^[2] Fdn Publ Galega Med Xen, CIBERER, Grp Med Xen USC, Santiago De Compostela, Galicia - Spain

^[3] Univ Sao Paulo, Univ Hosp, BR-09500900 Sao Paulo - Brazil

^[4] Inst Dante Pazzanese Cardiol, Sao Paulo - Brazil

^[5] Complexo Hosp Santiago de Compostela, Galicia - Spain

• Document type: Journal article
• Source: Clinica Chimica Acta; v. 417, p. 8-11, FEB 18 2013.
• Web of Science Citations: 19

Abstract

Objective: Using candidate gene approach, we have investigated the effect of single nucleotide polymorphism (SNP) in genes related to lipid metabolism and atherosclerosis on dyslipidemia and atorvastatin response. Methods: The study included 157 patients treated with atorvastatin and 145 controls. Genomic DNA was isolated and genotyped using SNPlex technology. Results: Allele and genotype disease association test revealed that APOB rs693 (OR: 2.2 {[}1.5-3.2], p = 0.0001) and CD36 rs1984112 (OR: 3.7 {[}1.9-7.0], p = 0.0002) SNPs were independent risk factors for hypercholesterolemia. Only APOB rs693 T variant allele was associated with increased LDL cholesterol levels (> 160 mg/dL). After atorvastatin treatment (10 mg/day/4 weeks), LIPC - 514T allele was positively associated with LDL cholesterol reduction. Conclusion: The current study reinforces the current knowledge that carrying APOB rs693 is an independent risk factor for dyslipidemia and higher LDL levels. Furthermore, we found that a variant of CD36 was associated with dyslipidemia as a risk (rs1984112) factor. Finally, atorvastatin response could be predicted by LIPC - 514C>T SNP and physical activity. In conclusion, our data evidences the contribution of genetic markers and their interaction with environmental factor in the variability of statin response. (c) 2012 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 08/06667-9 - Association study of 230 polymorphisms in 60 candidate genes and response to atorvastatin
• Grantee: Rosario Dominguez Crespo Hirata
• Support Opportunities: Regular Research Grants