systematic functional characterization of cytochrome p450 2e1 promoter variants in the chinese han population系统功能特性的细胞色素p450 2 e1子变异在中国汉族人群.pdf

Systematic Functional Characterization of Cytochrome P450 2E1 Promoter Variants in the Chinese Han Population 1,2. 1,2. 1,2 3 4 4 1,2 Xunyi Huang , Lili Chen , Wenlong Song , Ling Chen , Jiamin Niu , Xia Han , Guoyin Feng , Lin He1,2,5*, Shengying Qin1,2* 1 Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China, 2 Shanghai genomePilot Institutes for Genomics and Human Health, Shanghai, China, 3 School of Life Science and Technology, Shanghai Jiao Tong University, Shanghai, China, 4 Laiwu Hospital, Shandong, China, 5 Institutes of Biomedical Sciences, Fudan University, Shanghai, China Abstract CYP2E1 promoter polymorphisms can lead to significant interindividual differences in expression of CYP2E1. Using a database of CYP2E1 gene polymorphisms established in 2010, our study aimed to functionally characterize the single nucleotide polymorphisms (SNPs) of the promoter region and corresponding haplotypes in the Chinese Han population. Six novel SNPs and seven haplotypes with a frequency equal to or greater than 0.01 were constructed on a luciferase reporter system on the basis of site-directed mutagenesis. Dual luciferase reporter systems were used to analyze regulatory activity. The constructs including single novel SNP mutations exhibited insignificant change in luciferase activity, whereas, the activity produced by Haplo1(GTTGCTATAT), Haplo2 (CTTGCTATAT) and Haplo7 (GAGCTCACAT), containing a 2333T.A polymorphism was significantly greater than for the wild type in Hep G2 cells (p,0.