Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
Toxicol Mech Methods. 2012 Jul;22(6):461-5. doi: 10.3109/15376516.2012.672481.
Flavin-containing monooxygenases (FMOs) represent the second most important human monooxygenase system, after cytochrome P450s (CYPs) and catalyze the oxygenation of many chemicals containing nitrogen-, sulphur-, phosphorous-, selenium- and other nucleophilic heteroatoms. FMO3 is the prominent FMO form in adult human liver. For FMO3, both interindividual variability within a single ethnic group and variability between ethnic groups have been reported. In our study, three prevalent functional FMO3 variants (E158K, V257M, and E308G) were genotyped in healthy Turkish people by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) methods. The frequencies of alleles and haplotypes were compared with those obtained from different populations. It was found that FMO3 158K, 257M and 308G alleles, demonstrate impaired metabolism toward many FMO3 substrates, were observed frequently in Turkish population similar to the other populations. Also, the frequencies of haplotypes were determined based on individual allelic frequencies and it was observed that the most common haplotypes were haplotip EVE and KVE (E158K/V257M/E308G), which together accounted for 80% of all haplotypes. The obtained data from the present study could be useful for further studies assessing sensitivity to therapeutic drugs, environmental toxicants and common disease.
黄素单加氧酶（FMOs）是仅次于细胞色素 P450（CYPs）的第二大人类单加氧酶系统，可催化多种含氮、硫、磷、硒和其他亲核杂原子的化合物的氧化。FMO3 是成人肝脏中主要的 FMO 形式。对于 FMO3，已经报道了同一民族内个体间的变异性和不同民族间的变异性。在我们的研究中，通过聚合酶链反应（PCR）-限制性片段长度多态性（RFLP）方法，对健康的土耳其人群中的三种常见功能性 FMO3 变体（E158K、V257M 和 E308G）进行了基因分型。比较了等位基因和单倍型的频率与从不同人群中获得的频率。结果发现，FMO3 158K、257M 和 308G 等位基因对许多 FMO3 底物的代谢能力受损，在土耳其人群中与其他人群一样频繁出现。此外，还根据个体等位基因频率确定了单倍型频率，观察到最常见的单倍型是 EVE 和 KVE 单倍型（E158K/V257M/E308G），它们共同占所有单倍型的 80%。本研究获得的数据可用于进一步评估治疗药物、环境毒物和常见疾病敏感性的研究。
