A prospective study of polymorphisms of DNA repair genes XRCC1, XPD23 and APE/ref-1 and risk of stroke in Linxian, China.

Abstract

BACKGROUND:

Stroke is the leading cause of death in Linxian, China. Although there is evidence of DNA damage in experimental stroke, no data exist on DNA repair and stroke in human populations.

AIM:

To assess the risk of stroke conferred by polymorphisms in the DNA repair genes, XRCC1, XPD23 and APE/ref-1 in a cohort of individuals originally assembled as subjects in two cancer prevention trials in Linxian, China.

METHODS:

The subjects for this prospective study were sampled from a cohort of 4,005 eligible subjects who were alive and cancer free in 1991 and had blood samples available for DNA extraction. Using real-time Taqman analyses, all incident cases of stroke (n = 118) that developed from May 1996, and an age- and a sex-stratified random sample (n = 454) drawn from all eligible subjects were genotyped. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% CIs.

RESULTS:

No association was observed between polymorphisms in APE/ref-1 codon 148 and XRCC16 codon 194, and stroke. Polymorphisms in XRCC110 codon 399 were associated with a significantly reduced risk of stroke (RR 0.59, 95% CI 0.36 to 0.96, p = 0.033), whereas XPD23 codon 312 was associated with a significantly increased risk of stroke (RR 2.18, 95% CI 1.14 to 4.17, p = 0.010).

CONCLUSIONS:

Polymorphisms in DNA repair genes may be important in the aetiology of stroke. These data should stimulate research on DNA damage and repair in stroke.

• Authors: Somdat Mahabir, Christian C Abnet, You-Lin Qiao, Luke D Ratnasinghe, Sanford M Dawsey, Zhi-Wei Dong, Philip R Taylor, Steven D Mark
• Journal: Journal of epidemiology and community health (J Epidemiol Community Health) Vol. 61 Issue 8 Pg. 737-41 (Aug 2007) ISSN: 0143-005X [Print] England
• PMID: 17630376 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Codon
• DNA-Binding Proteins
• X-ray Repair Cross Complementing Protein 1
• XRCC1 protein, human
• Xeroderma Pigmentosum Group D Protein
• APEX1 protein, human
• DNA-(Apurinic or Apyrimidinic Site) Lyase
• ERCC2 protein, human

Topics

• China (epidemiology)
• Codon (genetics)
• DNA Repair (genetics)
• DNA-(Apurinic or Apyrimidinic Site) Lyase (genetics)
• DNA-Binding Proteins (genetics)
• Female
• Gene Frequency (genetics)
• Genotype
• Humans
• Linkage Disequilibrium (genetics)
• Male
• Middle Aged
• Polymorphism, Genetic (genetics)
• Prospective Studies
• Risk Factors
• Stroke (epidemiology, genetics)
• X-ray Repair Cross Complementing Protein 1
• Xeroderma Pigmentosum Group D Protein (genetics)