Polymorphisms in the thymidylate synthase promoter and the DNA repair genes XRCC1 and XPD in a Brazilian population

Abstract

Polymorphisms in genes responsible for maintaining genomic integrity are potential modifiers of disease risk. Since considerable interindividual and interethnic variation in DNA repair capacity has been associated with polymorphic alleles, we evaluated the frequency of the 2R/3R variants in the TS promoter, Arg194Trp and Arg399Gln in the XRCC1 gene, and Asp312Asn and Lys751Gln in the XPD gene in 364 healthy individuals from a Brazilian population separated by ethnicity (European ancestry and African ancestry). The genotypes were determined by PCR (TS) or by PCR-RFLP (XRCC1 and XPD). The frequency of the TS 3R allele was 0.56 for whites and 0.51 for nonwhites. In the case of the XRCC1 MspI polymorphism, the allele frequencies were 0.09 for 194Trp in both nonwhites and whites and 0.27 and 0.28 for 399Gln in nonwhites and whites, respectively. For the XPD 312Asn allele, we found a frequency of 0.25 in white individuals, which was significantly different (P = 0.025) from that seen in nonwhites (0.15). Similarly, the 751Gln polymorphic allele of the XPD gene was significantly more frequent (P < 0.002) in whites (0.30) than in nonwhites (0.20). The genotype frequencies were within Hardy-Weinberg equilibrium. We concluded that the genotype and allele frequencies of XPD gene polymorphism differed between white and nonwhite Brazilians, and that the frequencies of the XPD 312Asn and XRCC1 399Gln alleles in this Brazilian population showed ethnic variability when compared with those observed in other populations.