Jenny Lagos1, Tomás Zambrano, Alexy Rosales, Luis A Salazar. 1. Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera (BIOREN-UFRO), Av. Francisco Salazar 01145, Casilla 54-D, 4811230, Temuco, Chile.
Abstract
BACKGROUND AND OBJECTIVES: This study evaluated the influence of the polymorphisms G1784C (rs4822063) and A2386G (rs12487736) of SREBP-2 and SCAP genes, respectively, on the response to atorvastatin treatment in a cohort of Chilean subjects with Amerindian background. METHODS: A total of 142 hypercholesterolemic individuals underwent atorvastatin therapy (10 mg/day/1 month). Serum lipids levels before and after treatment were measured. Genotyping of the studied polymorphisms and ethnic characterization through Amerindian haplogroups (A, B, C, and D) of mitochondrial DNA was achieved by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP), respectively. RESULTS: Of all individuals, 85 % turned out to be Amerindian. C allele carriers for polymorphism G1784C, had a lower total cholesterol reduction (p = 0.015) and low-density lipoprotein cholesterol (LDL-C) (p = 0.013). No differences were found for the A2386G variant. However, those who carried both polymorphisms had a lower LDL-C reduction than carriers of just one of the variants (p = 0.030). CONCLUSION: The G1784C polymorphism of SREBP-2 gene affects atorvastatin response in Chilean subjects with Amerindian background, and may be an important marker for predicting efficacy of lipid-lowering therapy.
BACKGROUND AND OBJECTIVES: This study evaluated the influence of the polymorphisms G1784C (rs4822063) and A2386G (rs12487736) of SREBP-2 and SCAP genes, respectively, on the response to atorvastatin treatment in a cohort of Chilean subjects with Amerindian background. METHODS: A total of 142 hypercholesterolemic individuals underwent atorvastatin therapy (10 mg/day/1 month). Serum lipids levels before and after treatment were measured. Genotyping of the studied polymorphisms and ethnic characterization through Amerindian haplogroups (A, B, C, and D) of mitochondrial DNA was achieved by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP), respectively. RESULTS: Of all individuals, 85 % turned out to be Amerindian. C allele carriers for polymorphism G1784C, had a lower total cholesterol reduction (p = 0.015) and low-density lipoprotein cholesterol (LDL-C) (p = 0.013). No differences were found for the A2386G variant. However, those who carried both polymorphisms had a lower LDL-C reduction than carriers of just one of the variants (p = 0.030). CONCLUSION: The G1784C polymorphism of SREBP-2 gene affects atorvastatin response in Chilean subjects with Amerindian background, and may be an important marker for predicting efficacy of lipid-lowering therapy.
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