title: Genotype‑phenotype analysis of CYP2C19 in the Tibetan population and its potential clinical implications in drug therapy.
abstract: Cytochrome P450 2C19 (CYP2C19) is a highly polymorphic gene, it codes for a protein responsible for the metabolism of multiple clinically important therapeutic agents. However, there is currently no available data on the distribution of CYP2C19 mutant alleles in the Tibetan population. The aim of the present study was to identify different CYP2C19 mutant alleles and determine their frequencies, along with genotypic frequencies, in the Tibetan population. The whole CYP2C19 gene was amplified and sequenced in 96 unrelated, healthy Tibetans from the Tibet Autonomous Region of China, the promoter region, exons, introns and the 3'‑UTR were screened for genetic variants. Three novel genetic polymorphisms in CYP2C19 were detected among a total of 27 different mutations. The allele frequencies of CYP2C19*1A, *1B, *2A, *3A and *17 were 50, 28.13, 15.10, 5.21 and 1.56%, respectively. The most common genotype combinations were CYP2C19*1A/*1B (56.25%) and *1A/*2A (30.21%). One novel non‑synonymous mutation (Asn to Lys) in CYP2C19 was identified, and this mutation was predicted to be intolerant and benign by SIFT and PolyPhen‑2, respectively. The observations of the present study may have important clinical implications for the use of medications metabolized by CYP2C19 among Tibetans.
authors.affiliation: Key Laboratory of High Altitude Environment and Genes Related to Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, P.R. China.
authors.forename: Tianbo
authors.initials: T
authors.lastname: Jin
authors.affiliation: School of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, P.R. China.
authors.forename: Xiyang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Geng
authors.affiliation: Key Laboratory of High Altitude Environment and Genes Related to Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, P.R. China.
authors.forename: Xugang
authors.initials: X
authors.lastname: Shi
authors.affiliation: Key Laboratory of High Altitude Environment and Genes Related to Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of High Altitude Environment and Genes Related to Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, P.R. China.
authors.forename: Dongya
authors.initials: D
authors.lastname: Yuan
authors.affiliation: Key Laboratory of High Altitude Environment and Genes Related to Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, P.R. China.
authors.forename: Longli
authors.initials: L
authors.lastname: Kang
mesh_terms: D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D004358:Drug Therapy; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012984:Software; D018609:Tibet
chemical_list: D065731:Cytochrome P-450 CYP2C19