Arnaldo Paulo, Thompson Ricardo Estevão, Lopes Márcia Quinhones, Suffys Philip Noel, Santos Adalberto Rezende
Platform of Parasitology, Ministry of Health, National Institute of Health, P.O.Box 264 - Maputo, Mozambique.
Malays J Med Sci. 2013 Jul;20(4):13-23.
The cytochrome P450 enzymes (CYP) play an important role in the metabolism of many therapeutic agents. The activities of different enzymes exhibit variability in different populations, which causes variations in drug response or toxicity. The CYP2B6 and CYP2C8 enzymes are encoded by polymorphic genes characterised by different single nucleotide polymorphisms (SNPs). Several of these CYP variants are often associated with slow metabolism phenotypes. This study aimed to analyse the frequencies of allelic variants of CYP2B6 and CYP2C8 in the Mozambican population.
Using a polymerase chain reaction and restriction fragment length polymorphism assay (PCR-RFLP), the frequencies of the allelic variants of CYP2B6 (c.64C>T, c.516G>T, c.777C>A, c.785A>G, c.1459C>T) and CYP2C8 (c.805A>T, c.416G>A, c.1196A>G, c.792C>G) were determined in 360 Mozambican blood donors.
The frequencies of the allelic variants of the CYP2B6 gene were 0.057, 0.426, 0.0, 0.410, and 0.004. For the CYP2C8 gene, the frequencies of the allelic variants were 0.160, 0.048, 0.0, and 0.005. No significant differences were observed between the gender and geographic distribution of volunteers around the country.
The frequencies of the allelic variants of the CYP2B6 and CYP2C8 genes were found to be homogeneously distributed in the Mozambican population and were comparable to other African populations. Further studies are required to explore the impact of these variants on the clinical response (efficacy and toxicity) of drugs, including antimalarials.
细胞色素P450酶(CYP)在许多治疗药物的代谢中起重要作用。不同酶的活性在不同人群中表现出变异性,这导致药物反应或毒性的差异。CYP2B6和CYP2C8酶由具有不同单核苷酸多态性(SNP)的多态基因编码。这些CYP变体中的几种通常与代谢缓慢表型相关。本研究旨在分析莫桑比克人群中CYP2B6和CYP2C8等位基因变体的频率。
使用聚合酶链反应和限制性片段长度多态性分析(PCR-RFLP),在360名莫桑比克献血者中测定CYP2B6(c.64C>T、c.516G>T、c.777C>A、c.785A>G、c.1459C>T)和CYP2C8(c.805A>T、c.416G>A、c.1196A>G、c.792C>G)等位基因变体的频率。
CYP2B6基因等位基因变体的频率分别为0.057、0.426、0.0、0.410和0.004。对于CYP2C8基因,等位基因变体的频率分别为0.160、0.048、0.0和0.005。在该国志愿者的性别和地理分布之间未观察到显著差异。
发现CYP2B6和CYP2C8基因等位基因变体的频率在莫桑比克人群中分布均匀,并且与其他非洲人群相当。需要进一步研究以探索这些变体对包括抗疟药在内的药物临床反应(疗效和毒性)的影响。