Hao DaCheng, Sun Jie, Furnes Bjarte, Schlenk Daniel, Li MiaoXin, Yang ShengLi, Yang Ling
Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Cell Biochem Funct. 2007 Jul-Aug;25(4):443-53. doi: 10.1002/cbf.1326.
The aims of this study were to analyze flavin-containing monooxygenase 3 (FMO3) polymorphisms and allele and genotype frequencies in 256 Han Chinese and 50 African-American individuals, to compare the allele and genotype frequencies of these populations with those of other world populations. For Han Chinese, genotyping of three common single nucleotide polymorphisms, E158K, V257M and E308G was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). For African-Americans, genotyping of all coding exons was performed by modified PCR-single strand conformational polymorphism (SSCP). Evolutionary rates of FMO3 were estimated computationally. We found that there were significant differences in allele and genotype frequencies among Han Chinese, African-Americans and other world populations. In Han Chinese, the minor allele frequencies (MAFs) were 0.229 (E158K), 0.203 (V257M) and 0.148 (E308G), respectively. In African-Americans, MAFs were 0.48 (E158K), 0.05 (V257M) and 0 (E308G), respectively. There was rapid evolution during the divergence of primate FMO3. This is the first report comparing FMO alleles and genotypes between Han Chinese and African-Americans. A Han Chinese population database has been established for three gene polymorphisms. The data presented here justify further pharmacogenetic studies for potentially optimizing recommended drug dosages and evaluating relationships with disease processes.
本研究的目的是分析256名汉族人和50名非裔美国人中含黄素单加氧酶3(FMO3)的多态性、等位基因和基因型频率,并将这些人群的等位基因和基因型频率与其他世界人群进行比较。对于汉族人,通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对三种常见单核苷酸多态性E158K、V257M和E308G进行基因分型。对于非裔美国人,通过改良的PCR-单链构象多态性(SSCP)对所有编码外显子进行基因分型。通过计算估计FMO3的进化速率。我们发现汉族人、非裔美国人和其他世界人群之间的等位基因和基因型频率存在显著差异。在汉族人中,次要等位基因频率(MAF)分别为0.229(E158K)、0.203(V257M)和0.148(E308G)。在非裔美国人中,MAF分别为0.48(E158K)、0.05(V257M)和0(E308G)。灵长类FMO3分化过程中存在快速进化。这是第一篇比较汉族人和非裔美国人FMO等位基因和基因型的报告。已建立了一个包含三种基因多态性的汉族人群数据库。此处提供的数据为进一步开展药物遗传学研究以潜在优化推荐药物剂量并评估与疾病进程的关系提供了依据。