Abstract
Background The human CYP2B subfamily consists of one functional gene (CYP2B6) and one pseudogene (CYP2B7P). Cytochrome P450 2B6 (CYP2B6) is a highly polymorphic enzyme that shows marked interindividual and interethnic variations. Currently, 38 alleles have been described, and some of the allelic variants have been associated with low enzyme activity. The aim of this study was to investigate the frequencies of CYP2B6∗4, CYP2B6∗5, and CYP2B6∗6 alleles in the Mazani ethnic group among Iranian Population. Methods The study was conducted in 289 unrelated healthy volunteers. DNA was extracted from peripheral blood and analyzed by the PCR-RFLP protocol. The PCR product was digested with restriction enzymes and then separated using agarose gel electrophoresis. Results The frequency of CYP2B6∗4, CYP2B6∗5, and CYP2B6∗6 in this study was 34.60%, 7.26%, and 34.54%, respectively. Conclusion The frequency of the CYP2B6∗4 allele in the Mazani ethnic group was much higher (34.60%) than other population. The frequency of CYP2B6∗6 (34.54%) also was higher than its frequency in other previously reported population. But the frequency of CYP2B6∗5 in this study was lower than expected. These results will be useful in understanding the ethnic diversity in Iranian population and offer a preliminary basis for more rational use of drugs that are substrates for CYP2B6 in this population.
Highlights
Polymorphisms are the cause of 15–30% of individual difference in the drug metabolism [1, 2]. e human CYP is a supergene family which is expressed in the liver. 57 polymorphic genes containing a large number of SNVs and CNVs belong to this supergene family [3]
We examined the frequencies of Cytochrome p402B6 (CYP2B6)∗4, CYP2B6∗5, and ∗6 mutant alleles in the Mazani ethnic group among Iranian population
Frequencies of the three polymorphisms including CYP2B6∗4, CYP2B6∗5, CYP2B6∗6 in 289 individuals are provided in Table 3. e frequency of polymorphic CYP2B6 alleles responsible for impaired drug metabolisms CYP2B6∗4, ∗5, and ∗6 was 34.60%, 7.26%, and 34.54%, respectively (Table 3)
Summary
Polymorphisms are the cause of 15–30% of individual difference in the drug metabolism [1, 2]. e human CYP is a supergene family which is expressed in the liver. 57 polymorphic genes containing a large number of SNVs and CNVs belong to this supergene family [3]. Cytochrome p402B6 (CYP2B6) is known as one of the important subclasses for drug metabolizing enzyme in the liver and other organs. Polymorphisms of this gene cause differences in transcriptional regulation, splicing, and expression of mRNA and protein [5]. E CYP2B6 gene is mainly expressed in the liver cells, where it makes about 3–5% of the total microsomal P450 pool [10,11,12] It is active at lower levels in extrahepatic tissues, including the intestine, kidney, lung, skin, and brain [13, 14]. The differences in gene regulation and genetic polymorphisms largely contribute to interindividual variability in CYP2B6 activity. We examined the frequencies of CYP2B6∗4 (rs2279343), CYP2B6∗5 (rs3211371), and ∗6 (rs3745274) mutant alleles in the Mazani ethnic group among Iranian population
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