| Single nucleotide polymorphism (SNP), the main form of genome variation, has become one of the current hotspots in Human Gnome Project, for it has essential applications in complex disease gene mapping and pharmacogenomics study. Metabolism, disposition and effect of drug and carcinogen are mediated by xenobiotic response related genes. Discovery and correlation or association study for SNPs in these genes are important parts of individualized treatment-oriented pharmacogenetics and population prevention-oriented genetic epidemiology of cancer.As pharmacogenetics part of the Chinese SNP project, this study contained three logical elements: Reference SNPs were firstly catalogued for 20 xenobiotic response genes in Chinese population. And linkage disequilibrium (LD) profile and haplotype structure for two ABC transporter genes (ABCC1, ABCG2) were resolved, as an example, with several LD blocks of low haplotype diversity in both loci, indicating that LD and haplotype analyses have useful implications for marker selection and study design in genetic association analysis. In pharmacogenetics study, SNP screening of one sample set with phenotyped HNMT (Histamine N-Methyltransferase) activity and genotype-phenotype correlation analysis were conducted. Some common SNPs at putative regulatory regions of HNMT were found to be correlated with phenotype only in female, indicating that estrogen or other sex-related hormones might mediate regulation of HNMT activity. In cancer genetic epidemiology study, one functionally characterized SNP (Arg257Cys) in CYP2A13 that codes the most active P450 for the metabolic activation of tobacco-specific carcinogen NNK, was found to be significantly associated with substantial reduction in risk of lung adenocarcinoma. The role of interaction between NNK and CYP2A13 in pulmonary carcinogenesis and the protective modification of lung adenocarcinoma risk by CYP2A13 Arg257Cys variant were documented for the first time at population level.
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