Prevalence of CYP2B6 polymorphisms in Argentinians: the role of genetic testing

Abstract

ABSTRACT. CYP2B6 is a highly polymorphic isoenzyme involved in the metabolism of many drugs including cyclophosphamide, bupropion, and efavirenz. A single nucleotide polymorphism (SNP) in CYP2B6 (516G>T) resulted in decreased expression and function associated with the CYP2B6*6 haplotype. Among the clinical implications of this phenotype, decreased activation of cyclophosphamide and increased plasma levels of efavirenz associated with increased central nervous system toxicity have been reported. The frequency of the CYP2B6 (516G>T) SNP has been studied in several different populations, but there is no data regarding distribution among Argentinians. In this study, 102 DNA samples from healthy volunteers were analyzed using a polymerase chain reactionrestriction fragment length polymorphism reaction specific for the CYP2B6 (516G>T) SNP. Our results showed a prevalence of 71.08% for the G allele and 28.92% for the T allele. This was distributed as 52.9% for the GG genotype (reduced dosage required), 36.6% for the GT genotype (normal dosage range), and 10.8% for the TT genotype (high drug toxicity). There was no preferential gender distribution observed. The relatively high 16595©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 16594-16599 (2015) CYP2B6 polymorphisms and the role of genetic testing prevalence of the TT genotype in our population supports the clinical use of genotyping as an additional tool in personalized medicine.

Distribution of CYP2B6 516G/T pharmacogenetically important polymorphism in the Ukrainian population

“…Sexual differences in the distribution of genotypes were not observed. Genotyping should be used as an additional tool for personalized medicine in connection with the high prevalence of the TT genotype in the studied population (Scibona et al, 2015). The study conducted in China determined the frequency of CYP2B6 516G/T mutation in 79 HIV infected patients.…”

“…The CYP2B6 is one of the members of the cytochrome P450 superfamily. This enzyme metabolizes a number of currently prescribed drugs and different compounds, such as nicotine (Yamazaki et al, 1999), cyclophosphamide, bupropion, efavirenz (Scibona et al, 2015) and ketamine (Li et al, 2015).…”

“…A typical example of the single nucleotide polymorphism of the CYP2B6 with decreased enzymatic activity is the variant 516G/T relating to the CYP2B6∗6 allele. Phenotypically, the TT homozygotes are poor metabolizers (highly toxic drug), the GT heterozygotes are characterized by intermediate activity of the CYP2B6 enzyme (therapeutic dose of the drug is recommended), and the GG homozygotes are rapid metabolizers (increased dose of the drug is recommended) (Scibona et al, 2015).…”

“…Numerous studies point to the presence of clinical associations of the CYP2B6 variants. Thus, in poor metabolizers of the CYP2B6, the clinical consequences of taking drugs metabolized by the corresponding enzyme can be, for example, a delayed activation of cyclophosphamide and an increased level of efavirenz, which in turn can have a toxic effect on the central nervous system (Scibona et al, 2015). In particular, one study in China showed pharmacokinetic differences in HIV-infected patients with different genotypes of CYP2B6 516G/T who underwent antiviral therapy with efavirenz.…”

Cytochrome P450 CYP2B6*6 distribution among Congolese individuals with HIV, Tuberculosis and Malaria infection

“…In Africa, the overall frequency of the G and T alleles is 65% and 35%, respectively, and that of genotypes GG is 42%, GT is 45%, and TT is 13% (Scibona et al, 2015). Arnaldo et al demonstrated a large variation in the distribution of different CYP2B6 variants in Mozambique including the G516T substitution (Arnaldo et al, 2013).…”