title: Analysis of CYP3A4 genetic polymorphisms in Han Chinese.
abstract: Our study aimed to comprehensively investigate the genetic polymorphisms of CYP3A4 in Han Chinese. We sequenced the gene regions of CYP3A4, including its promoter, exons, surrounding introns and 3' untranslated region (3'UTR), from 100 unrelated-healthy Han Chinese individuals. We detected 11 SNPs, three of which are novel. According to in silico functional prediction of novel variants, 20148 A>G in exon 10, resulting in substitution of Tyr319 with Cys (CYP3A4*21), may induce dramatic alteration of protein conformation, and 26908 G>A in 3'UTR may disrupt post-transcriptional regulation. We identified five alleles in Han Chinese, the allele frequencies of CYP3A4*1, *5, *6, *18 and *21 are 97, 0.5, 1, 1 and 0.5%, respectively. Haplotype inference revealed 14 haplotypes, of which the major haplotype CYP3A4*1A constitutes 59% of the total chromosomes. We also examined the possible role of natural selection in shaping the variation of CYP3A4 and confirmed a trend, consistent with the action of positive selection. We systematically screened the genetic polymorphisms of CYP3A4 in Han Chinese, highlighted possible functional impairment of the novel allele and summarized the distinct allele and haplotype frequency distribution, with an emphasis on detecting the footprint of recent positive selection on the CYP3A4 gene in Han Chinese.
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China. zhouqingnwu@gmail.com
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yu
authors.forename: Chang
authors.initials: C
authors.lastname: Shu
authors.forename: Yimei
authors.initials: Y
authors.lastname: Cai
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.forename: Xumin
authors.initials: X
authors.lastname: Wang
authors.forename: Duen-mei
authors.initials: DM
authors.lastname: Wang
authors.forename: Songnian
authors.initials: S
authors.lastname: Hu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D002460:Cell Line; D051544:Cytochrome P-450 CYP3A / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008958:Models, Molecular; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011487:Protein Conformation; D034622:RNA Interference; D012641:Selection, Genetic; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human