Allele and Genotype Frequencies ofCytochrome P450 2B6Gene in a Mongolian Population

Abstract

ABSTRACT:CYP2B6 plays an important role in metabolizing various drugs in common clinical use. Increasing interest in CYP2B6 genetic polymorphism was stimulated by revelations of a specific CYP2B6 genotype significantly affecting the metabolism of efavirenz, an anti-HIV type-1 agent. The present study determined the CYP2B6 haplotype in 100 healthy unrelated Mongolian volunteers by analyzing the genotypes of nine single nucleotide polymorphism (SNP) positions (؊82T>C, 64C>T, 499C>T, 516G>T, 777C>A, 785A>G, 983T>C, 1375A>G, and 1459C>T) in the CYP2B6 gene. The CYP2B6 *1 allele was the most frequent in the Mongolian population tested at 64.5%, higher than the equivalent frequency in African-Americans and Ghanaians. The second most frequent allele was CYP2B6 *6 (21.0%), although this allele was less frequent than that in Ghanaians. Only one CYP2B6 *5 allele was identified in our Mongolian subjects (0.5%), although it is the third most frequent allele in white and African-American populations. These CYP2B6 genotypes revealed seven slow efavirenz metabolizers in 100 Mongolians, which is significantly fewer than the same group among Ghanaians. Overall, the Mongolian CYP2B6 allele distribution was comparable with that in Japanese, Koreans, and Han Chinese. This is the first report of CYP2B6 genotype frequency in a Mongolian population, and it could provide clinically useful information on drug metabolism in this population group.

Prevalence of poor and rapid metabolizers of drugs metabolized by CYP2B6 in North Indian population residing in Indian national capital territory

“…Analysis of the results based on frequency histogram and probit analysis revealed that 20.56% of the target population was poor metabolizer. The prevalence of poor metabolizers, which we observed in this study, was comparatively lower than West Africa (54%) (Malhotra et al 2006), Papua New Guinea (63%) (Malhotra et al 2006), Spain (40%) (Novoa et al 2005), Mongolian (35.5%) (Davalkham et al 2009), Japanese (32.6%) (Gatanaga et al 2007), Han Chinese (32.9%) (Guan et al 2006), African American (54.6%) (Klein et al 2005), Ghanians (59.7%) (Klein et al 2005), Caucasians (38.9%) (Blievernicht et al 2007) and Koreans (23.9%) (Klein et al 2005). In India, percentage of poor metabolizers was 40% in South Indian population (Ramachandran et al 2009).…”

“…Some of these variations are rare, but many are common, with allele frequencies between 10% and almost 50%, depending on the population (Klein et al 2005; Solus et al 2004). Ethnic or racial inter-individual CYP2B6 polymorphism in various populations has been reported in Caucasians (Lang et al 2001), Japanese (Hiratsuka et al 2002and Hiratsuka et al 2004), African-American-Hispanic (Lamba et al 2003; Hesse et al 2004), Korean (Cho et al 2004), Mongolian (Davalkham et al 2009), Spain (Novoa et al 2005), and South Indians (Ramachandran et al 2009), but not in North Indian population, and, hence, CYP2B6 was selected in this study.…”

Polymorphic Variants of Cytochrome P450 2B6 (CYP2B6.4–CYP2B6.9) Exhibit Altered Rates of Metabolism for Bupropion and Efavirenz: A Charge-Reversal Mutation in the K139E Variant (CYP2B6.8) Impairs Formation of a Functional Cytochrome P450-Reductase Complex

“…CYP2B6 is one of the most polymorphic cytochrome P450 genes becauseϳ100 single-nucleotide polymorphisms have been identified, and 29 of these single-nucleotide polymorphisms result in amino acid substitutions (http://www.cypalleles.ki.se). Some of the CYP2B6 alleles occur with relatively high frequencies across different populations; the allele frequency for CYP2B6*6 is approximately 21% in Mongolians, 28.2% in whites, 32.8% in African-Americans, and 62% in Papua New Guineans (Lang et al, 2001;Mehlotra et al, 2006;Davaalkham et al, 2009). CYP2B6*4 and CYP2B6*5 occur more frequently among the Han Chinese (9.1%) and whites (12.2%), respectively, than other ethnic populations (Jacob et al, 2004;Guan et al, 2006).…”

Genetic variation in the CYP2B6 Gene is related to circulating 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47) concentrations: an observational population-based study

“…Several single nucleotide polymorphisms (SNPs) in the P450 system have been reported to influence the activity of different CYP enzymes that are important for metabolism of both endogenous, exogenous and xenobiotic compounds [21,25,26]. For example, a specific genotype in CYP2B6 has been shown to affect the xenobiotic metabolism of an anti-HIV agent [27]. Also, effects of certain SNPs have been reported, for example rs2279345 was found to be associated with a higher clearance and a lower plasma concentration of methadone [28].…”