Cytochrome P450 CYP2B6 genotypes and haplotypes in a Colombian population: identification of novel variant CYP2B6 alleles

被引：8
作者：
Gonzalo Restrepo, Juan [1 ,5 ]
Martinez, Carmen [1 ]
Garcia-Agundez, Augusto [3 ]
Gaviria, Elmer [5 ]
Julio Laguna, Jose [4 ]
Garcia-Martin, Elena [2 ]
Agundez, Jose A. G. [1 ]
机构：
[1] Univ Extremadura, Dept Pharmacol, E-06071 Badajoz, Spain
[2] Univ Extremadura, Dept Biochem, E-06071 Badajoz, Spain
[3] AMGenomics, Caceres, Spain
[4] Cent Hosp Cruz Roja, Madrid, Spain
[5] Univ Antioquia, Medellin, Colombia
来源：
PHARMACOGENETICS AND GENOMICS | 2011年 / 21卷 / 12期
关键词：
CYP2B6; mixed population; polymorphisms; EFAVIRENZ PLASMA-CONCENTRATIONS; INTRAETHNIC VARIABILITY; SUBSTRATE-SPECIFICITY; METABOLISM; GENE; POLYMORPHISM; EXPRESSION; FREQUENCIES; P4502B6; PHARMACOKINETICS;
D O I：
10.1097/FPC.0b013e32834b3efc
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
Objective Information on CYP2B6 allele frequencies and detrimental genotypes in mixed human populations is scarce. The aim of this study was to analyze the frequencies and haplotypes of nonsynonymous CYP2B6 single nucleotide polymorphisms (SNPs) in a Colombian population. Methods One hundred and fifty-two healthy individuals were analyzed for five nonsynonymous CYP2B6 SNPs, namely rs8192709, rs3745274, rs2279343 rs28399499, and rs3211371. Results Besides eight known variant alleles, we identified two as yet unknown variant alleles combining, respectively, the SNPs rs3745274 and rs3211371 and rs8192709 and rs3745274. Comparison of Colombian mestizo individuals with other mestizo population indicates statistically significant differences (P < 0.001) for the gain-of-function CYP2B6*4 allele and for combined detrimental CYP2B6 alleles. In addition, we observed a low linkage between the SNPs rs3745274 and rs2279343, which are often assumed as linked. Conclusion In conclusion, large interethnic and intraethnic variability exists for CYP2B6 polymorphisms, thus reinforcing the need for tailored genotyping protocols for CYP2B6 testing as a biomarker of drug response. Pharmacogenetics and Genomics 21:773-778 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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收藏
页码：773 / 778
页数：6
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