Large-scale SNPs Discovery In Chinese And Genetic Susceptibility Of Persistent HBV Infection

Large-scale single nucleotide polymorphisms (SNPs) discovery in Chinese and applying these SNPs to the common diseases gene mapping and pharmacogenomics is one of the key important aims of national human functional genomics project presently. In the present study, we established technical platforms for large-scale SNP discovery, genotyping and genetic analysis, respectively. By using these platforms, we screened SNPs systematically in the 128 functionally important genes in Chinese individuals, and then examined the relationship between SNP markers in these genes and susceptibility to persistent HBV infection in Chinese population, through case-control and/or transmission/disequilibrium test (TDT). The main results of our study including: (1) We successfully established technical platforms for SNP discovery, genotyping and genetic analysis, respectively; (2) Large-scale SNPs screening of all exons, relevant exon-intron boundaries and ~2 kb promoter regions of 128 candidate genes was performed, and more than 1370 SNPs were identified. On the basis of the genotype data from these SNPs, haplotype assignment, linkage disequilibrium (LD) mapping and haplotype-tagged SNPs (htSNPs) determination for each gene were performed; (3) IL13, which is a susceptibility gene for asthma, is characterized by unusual haplotype structure and polymorphism pattern in Chinese and Caucasian population. This unusual pattern suggests that positive selection that acts in Chinese and Caucasian population may have played a role in establishing present-day variation at the IL13 locus; (4) The G6624A polymorphism in the IL12A 3'UTR (OR = 1.4, 95%CI = 1.1-1.7, P = 0.003), A-559C polymorphism in the IL18BP promoter (OR = 2.0, 95%CI = 1.3-2.9, P < 0.001) and T29C polymorphism in the exonl of ESR1 gene (OR = 1.39, 95% CI = 1.14-1.70, P = 0.001) showed significant associations with persistent HBV infection in Chinese population, respectively.Among the four main results, the first result, i.e. the SNP discovery, genotyping and genetic analysis pipeline, were established for the first time at home. The rest tliree results were reported for the first time both at home and abroad. The technical platforms established here and SNP catalogs constructed based on Chinese individuals can be used for common diseases gene mapping and pharmacogenomics studies. The identification of susceptibility genes for the chronicity of HBV infection may help future improved treatment and prevention of this disorder.