title: The association of XRCC1 haplotypes and chromosomal damage levels in peripheral blood lymphocyte among coke-oven workers.
abstract: Theoretically, a haplotype has a higher level of heterozygosity than individual single nucleotide polymorphism (SNP) and the association study based on the haplotype may have an increased power for detecting disease associations compared with SNP-based analysis. In this study, we investigated the effects of four haplotype-tagging SNPs (htSNP) and the inferred haplotype pairs of the X-ray cross-complementing group 1 (XRCC1) gene on chromosome damage detected by the cytokinesis-block micronucleus assay. The study included 141 coke-oven workers with exposure to a high level of polycyclic aromatic hydrocarbons and 66 nonexposed controls. The frequencies of total MN and MNed cells were borderline associated with the Arg(194)Trp polymorphism (P = 0.053 and P = 0.050, respectively) but not associated with the Arg(280)His, Arg(399)Gln and Gln(632)Gln polymorphisms among coke-oven workers. Five haplotypes, including CGGG, TGGG, CAGG, CGAG, and CGGA, were inferred based on the four htSNPs of XRCC1 gene. The haplotype CGGG was associated with the decreased frequencies of total MN and MNed cells, and the haplotypes TGGG and CGAG were associated with the increased frequencies of total MN and MNed cells with adjustment for covariates among coke-oven workers. This study showed that the haplotypes derived from htSNPs in the XRCC1 gene were more likely than single SNPs to correlate with the polycyclic aromatic hydrocarbon-induced chromosome damage among coke-oven workers.
authors.affiliation: National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, 29 Nanwei Road, 100050 Beijing, China.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Leng
authors.forename: Juan
authors.initials: J
authors.lastname: Cheng
authors.forename: Linyuan
authors.initials: L
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Niu
authors.forename: Yufei
authors.initials: Y
authors.lastname: Dai
authors.forename: Zufei
authors.initials: Z
authors.lastname: Pan
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Fengsheng
authors.initials: F
authors.lastname: He
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000395:Air Pollutants, Occupational / Q000097:blood / Q000633:toxicity*; D002681:China; D003077:Coke / Q000633:toxicity*; D003430:Cross-Sectional Studies; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D008875:Middle Aged; D011084:Polycyclic Aromatic Hydrocarbons / Q000097:blood / Q000633:toxicity* / Q000652:urine; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012044:Regression Analysis; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D000395:Air Pollutants, Occupational; D003077:Coke; D004268:DNA-Binding Proteins; D011084:Polycyclic Aromatic Hydrocarbons; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human