Interethnic variability of ERCC2 polymorphisms

Pharmacogenomics J. 2005;5(1):54-9. doi: 10.1038/sj.tpj.6500283.

Abstract

Excision Repair Cross-Complementing Rodent Repair Group 2 (ERCC2) plays an important role in DNA repair by eliminating bulky DNA adducts produced by platinum agents during the nucleotide excision repair pathway. Several studies have associated polymorphisms in ERCC2 with response to platinum therapy, lung cancer risk, and DNA repair capacity. This study examined ERCC2 polymorphisms and haplotype structure across 18.9 kb in 95 European, 95 African, and 95 Asian individuals. Single-nucleotide polymorphisms (SNPs) (ERCC2 -9164 A>T, -1989 A>G, -516 G>A, 468 C>A [Arg156Arg], 1737 C>T [Val579Val], 2133 C>T [Asp711Asp], and 2251 T>G [Lys751Gln]) were mined and mapped using Golden Path, PolyMAPr, and Promolign. Genotyping was performed using PCR and pyrosequencing. Allele frequencies ranged from 0 to 0.47 (Europeans), 0.05 to 0.72 (Africans), and 0 to 0.47 (Asians). The synonymous cSNP at codon 579 could not be confirmed in our populations. There were significant differences in haplotype structure and frequency between populations. This information on ERCC2 genomic structure will allow the construction of definitive studies to clarify the clinical role of this important gene.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • African Continental Ancestry Group / genetics
  • Aged
  • Aged, 80 and over
  • Asian Continental Ancestry Group / genetics
  • Continental Population Groups / ethnology*
  • Continental Population Groups / genetics*
  • DNA Helicases / genetics*
  • DNA-Binding Proteins / genetics*
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Variation / genetics*
  • Humans
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Transcription Factors / genetics*
  • Xeroderma Pigmentosum Group D Protein

Substances

  • DNA-Binding Proteins
  • Transcription Factors
  • DNA Helicases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human