title: Polymorphisms of DNA repair pathway genes and cigarette smoking in relation to susceptibility to large artery atherosclerotic stroke among ethnic Chinese in Taiwan.
abstract: OBJECTIVE
  Cigarette-smoking induced oxidative DNA damage to endothelial cells has been reported to play an etiological role in atherosclerosis development. Individual vulnerability to oxidative stress through smoking exposure and the ability to repair DNA damage, which plays a critical role in modifying the risk susceptibility of large artery atherosclerotic (LAA) stroke, is hypothesized. Thus, we examined the effect of genetic polymorphisms of DNA repair pathway genes and cigarette smoking in relation to risk susceptibility of LAA stroke.
  
  
  METHODS
  We enrolled 116 LAA stroke patients and 315 healthy controls from the Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan. Genotyping of polymorphisms of the OGG1 (Ser326Cys), XRCC1 (Arg399Gln), ERCC2 (Lys751Gln), and ERCC5 (Asp1104His) genes was performed and used to evaluate LAA stroke susceptibility.
  
  
  RESULTS
  Of those non-synonymous polymorphisms, the ERCC2 Lys751Gln variant was found to be associated with LAA stroke risk (OR: 1.69, 95%CI: 1.02-2.86), and this association was more pronounced in smokers, manifesting a 2.73-fold increased risk of LAA stroke (p=0.027). A joint effect on risk elevation of LAA stroke was seen in those patients with OGG1 and ERCC2 polymorphisms (OR: 2.75, 95%CI: 1.26-6.00). Moreover, among smokers carrying the OGG1 Ser326Cys polymorphism, there was a tendency toward an increased risk of LAA stroke in those patients who had a greater number of high-risk genotypes of XRCC1, ERCC2, and ERCC5 polymorphisms (p(trend)=0.010).
  
  
  CONCLUSIONS
  The susceptible polymorphisms of DNA repair pathway genes may have a modifying effect on the elevated risk of LAA stroke in smokers among ethnic Chinese in Taiwan.
authors.affiliation: Section of Neurology, Department of Internal Medicine, Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Hann-Yeh
authors.initials: HY
authors.lastname: Shyu
authors.forename: Jia-Ching
authors.initials: JC
authors.lastname: Shieh
authors.forename: Lin
authors.initials: L
authors.lastname: Ji-Ho
authors.forename: Hsiao-Wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Chun-Wen
authors.initials: CW
authors.lastname: Cheng
mesh_terms: D050197:Atherosclerosis / Q000150:complications / Q000235:genetics*; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000235:genetics*; D020521:Stroke / Q000150:complications / Q000235:genetics*; D013624:Taiwan; D014026:Nicotiana