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International Journal of Morphology

On-line version ISSN 0717-9502

Abstract

ROSALES, Alexy et al. Frequency of Common Variants in Genes Involved in Lipid-Lowering Response to Statins in Chilean Subjects with Hypercholesterolemia. Int. J. Morphol. [online]. 2011, vol.29, n.4, pp.1296-1302. ISSN 0717-9502.  http://dx.doi.org/10.4067/S0717-95022011000400037.

Interindividual differences in activity and expression of the metabolizing enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P-glycoprotein (P-gp, encoded by ABCB1 gene) contribute considerably to lipid-lowering efficacy of statin treatment in subjects with hypercholesterolemia. Variability in the activity of CYP3A4, CYP3A5 and P-gp could be considered to result from genetic polymorphisms encoding their genes. However, the available data indicate that the frequencies of ABCB1, CYP3A4 and CYP3A5 gene polymorphisms differ significantly across populations. Thus, the aim of the present study was to determine the allelic frequency of three common variants of these genes in Chilean individuals with primary hypercholesterolemia (HC) and controls. A total of 135 unrelated patients (44 ± 7 years old) with diagnosis of hypercholesterolemia (Total cholesterol 240 mg/dL) and 120 normolipidemic healthy controls (40 ± 10 years old; total cholesterol 200 mg/dL) were included in this study. The 3435C>T (MDR1), -290A>G (CYP3A4) and 6986A>G (CYP3A5) gene polymorphisms were analyzed by PCR-RFLP. The genotype distribution for 3435C>T variant of ABCB1 in HC patients (CC: 49%, CT: 37%, TT: 14%) and controls (CC: 41%, CT: 48%, TT: 11%) was comparable (P=0.186). Similarly, the genotype distribution for -290A>G polymorphism of CYP3A4 in HC subjects (AA: 73%, AG: 27%, GG: 0%) and controls (AA: 71%, AG: 29%, GG: 0%) was equivalent (P = 0.863). Finally, the genotype distribution for 6986A>G variant of CYP3A5 in HC individuals (AA: 4%, AG: 41%, GG: 55%) and controls (AA: 4%, AG: 47%, GG: 49%) was similar (P=0.594). The allelic frequencies of 3435C>T (ABCB1), -290A>G (CYP3A4) and 6986A>G (CYP3A5) polymorphisms are similar between Chilean HC patients and controls, and comparable to frequencies found in Asian populations.

Keywords : Polymorphisms; Statins; Hypercholesterolemia; ABCB1.

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