Vu Nhung Phuong, Ma Thuong Thi Huyen, Tran Ngoc Thi Bich, Huynh Hue Thi Thu, Nguyen Ton Dang, Nguyen Duong Thuy, Van Nong Hai, Lee Ming Ta Michael, Nguyen Ha Hai
Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.
Genomic Medicine Institute, Geisinger Health System, 100 North Academy Avenue, Danville, PA, 17822, USA.
Mol Biol Rep. 2018 Oct;45(5):893-900. doi: 10.1007/s11033-018-4235-3. Epub 2018 Jul 5.
Genetic variations in CYP2C9 are associated to inter-individual variability of drugs metabolism and response. The only report has been done previously mainly focusing on the common variant alleles of CYP2C9 in Vietnamese Kinh subjects. However, little is known about the complete spectrum of this gene polymorphism in different ethnic groups of Vietnam. We sequenced the promoter region and all exons of CYP2C9 in 100 healthy unrelated Vietnamese Kinh subjects. Additionally, common CYP2C9 variants, 2 and 3, were also analyzed by RFLP-PCR in extra 194 Kinh subjects and 279 of other four ethnic groups in Vietnam. The results of these common variants observed from five ethnic groups were compared with other populations in the world. Seven previously reported alleles and two genotypes were determined in Kinh subjects. The percentage of CYP2C91 and CYP2C93 alleles are 96.5 and 3.5%, respectively. We found one novel non-synonymous variant in exon 7 leading to amino acid change at 363 position from proline to histidine. Functional analysis by SIFT and Polyphen-2 indicated that this mutation is intolerant and probably damaging. Prevalence of CYP2C9*2 observed in Vietnamese population was significantly lower compared with that of other populations in the South and West of Asia as well as in Europe. This study provides information of genetic distribution pattern of CYP2C9 in Vietnamese, which would be useful for optimizing drug therapies in Vietnam.
CYP2C9基因的遗传变异与药物代谢和反应的个体间差异相关。此前唯一的一份报告主要聚焦于越南京族人群中CYP2C9的常见变异等位基因。然而，关于越南不同民族该基因多态性的完整谱系却知之甚少。我们对100名健康无亲缘关系的越南京族受试者的CYP2C9启动子区域和所有外显子进行了测序。此外，还通过RFLP-PCR对另外194名京族受试者以及越南其他四个民族的279名受试者中的常见CYP2C9变异体2和3进行了分析。将这五个民族中观察到的这些常见变异体的结果与世界上其他人群进行了比较。在京族受试者中确定了7个先前报道的等位基因和2种基因型。CYP2C91和CYP2C93等位基因的百分比分别为96.5%和3.5%。我们在第7外显子中发现了一个新的非同义变异，导致363位氨基酸从脯氨酸变为组氨酸。SIFT和Polyphen-2的功能分析表明，该突变具有不耐受性且可能具有损害性。越南人群中观察到的CYP2C9*2的流行率与亚洲南部和西部以及欧洲的其他人群相比显著更低。本研究提供了CYP2C9在越南人群中的遗传分布模式信息，这将有助于优化越南的药物治疗。
