title: The DNA repair gene XPD/ERCC2 polymorphisms Arg156Arg (exon 6) and Lys751Gln (exon 23) are closely associated.
abstract: In the context of a molecular epidemiology study dealing with the effects of individual genetic susceptibility on childhood respiratory morbidity, DNA repair genotypes for the XPD/ERCC2 gene in exon 6 (Arg156Arg) and exon 23 (Lys751Gln) have been analyzed by PCR/RFLP assays in DNA samples isolated from the fetal parts of placentas. The study was performed using a cohort of 729 children born in 1994-1998 in two districts of the Czech Republic. On the basis of these data, we tested the association between the two genotypes. The principal finding of this study is that the exon 6 and exon 23 polymorphisms in the XPD/ERCC2 gene are tightly associated, with persons who are homozygous CC in exon 23 being mostly (81%) homozygous CC in exon 6, and persons homozygous AA in exon 6 mostly (88%) homozygous AA in exon 23. This strong association may have serious consequences for the interpretation of cancer susceptibility and other molecular epidemiology studies dealing with the XPD6 and XPD23 genotypes, since the observed effects of the silent XPD6 polymorphism might be, in fact, the result of XPD23 polymorphism, which is connected with an amino acid substitution in the resulting XPD protein.
authors.affiliation: Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4, Czech Republic. jtopinka@biomed.cas.cz
authors.forename: Jan
authors.initials: J
authors.lastname: Topinka
authors.forename: Irva
authors.initials: I
authors.lastname: Hertz-Picciotto
authors.forename: Miroslav
authors.initials: M
authors.lastname: Dostal
authors.forename: Irena
authors.initials: I
authors.lastname: Chvatalova
authors.forename: Poh-Sin
authors.initials: PS
authors.lastname: Yap
authors.forename: Caroline E W
authors.initials: CE
authors.lastname: Herr
authors.forename: Teri
authors.initials: T
authors.lastname: Greenfield
authors.forename: Radim J
authors.initials: RJ
authors.lastname: Sram
mesh_terms: D000293:Adolescent; D002648:Child; D015331:Cohort Studies; D018153:Czech Republic; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D005820:Genetic Testing; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012140:Respiratory Tract Diseases / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human