POLYMORPHISMS IN GENES CODING FOR MAJORDNA REPAIR PROTEINS XPC, XPD AND XRCC3 MAY MODULATE THE RISK OF CEREBROVASCULAR INCIDENTSIN THE BULGARIAN POPULATION
P. CHELENKOVA1,2, R. PETKOVA2, T. CHAMOVA3, S. ZHELIAZKOVA3, I. TOURNEV3, S. CHAKAROV1
1 – Department of Biochemistry, Faculty of Biology, Sofia University “St. KlimentOhridski”, Sofia, Bulgaria
2 – Scientific Technological Service Ltd., Sofia, Bulgaria
3 – Clinic of Neurology, University Hospital ‘Alexandrovska’, Sofia, Bulgaria
* Corresponding author: stoianchakarov@gmail.com
Keywords: DNA repair, individual repair capacity, genetic markers, risk assessment
Abstract: Eukaryotic cells are subjected daily to high levels of genotoxic damage. In young and healthy individuals the damage is normally promptly repaired. With age, the efficiency of DNA repair declines and the levels of unrepaired damage begin to grow, accelerating replicative quiescence and/or cell death in aged tissues. Carriership of variant alleles of genes coding for proteins responsible for DNA damage identification and repair may be associated with subtly deficient DNA repair and reduced capacity for cell and tissue renewal. The latter may increase the risk for development of degenerative disease.
This study analyses the association between carriership of variant alleles of common polymorphisms in genes coding for proteins functioning in nucleotide excision repair (XPC ins83, XPD (ERCC2) Lys751Gln), repair of breaks by homologous recombination (XRCC3 Thr241Met), damage-associated signalling and assessment of levels of damage (TP53 Pro72Arg) and the risk for cerebrovascular incidents in the Bulgarian population. There were statistically significant deviations from the Hardy-Weinberg equilibrium between the group of patients with cerebrovascular incidents and the controls for the markers XPC ins83, XPD Lys751Gln and XRCC3 Thr241Met. Concomitant carriership of the pro-apoptotic TP53 72Arg-allele together with ‚high-risk‘ variant alleles of the other three polymorphisms included in the study was significantly more common in patients with a history of cerebrovascular incidents than in healthy age-matched controls. Carriership of variant alleles of the polymorphisms XPC ins83, XPD Lys751Gln and XRCC3 Thr241Met and the pro-apoptotic 72Arg allele may constitute a risk factor for cerebrovascular incidents in the Bulgarian population.