The fine art of vascular wall maintenance. Carriership of XPC, TP53 and APOE polymorphisms may be a risk factor for cerebral vascular accidents in the Bulgarian population
Chelenkova, Pavlina | Petkova, Rumena | Chamova, Teodora | Zhelyazkova, Sashka | Tournev, Ivaylo | Chakarov, Stoyan
Efficient maintenance of the integrity of the endothelium of cerebral blood vessels is crucially important, especially when the vessel walls are subjected to greater-than-normal levels of stress. Persistently high levels of genotoxic stress may result from lower capacity to detect and repair DNA damage conferred by carriership of variants of key genes of DNA repair/maintenance of genomic integrity. Adult Bulgarian patients with a history of cerebral vascular accidents (CVAs) and age-matched healthy controls were analyzed for 11 markers, including 7 DNA polymorphisms in genes coding for proteins of DNA repair and maintenance of genomic integrity, 3 hypercoagulability markers and 1 marker for susceptibility for cerebral amyloidosis. Homozygous carriership of the del allele of the polymorphism XPCins83 was associated with decreased risk of CVAs (RR = 0.446, 95% CI:0.225–0.886, p = 0.021). In individuals carrying the 'protective' del/del XPCins83 genotype, carriership of the 'pro-apoptotic' genotype Arg/Arg in the TP53 locus was associated with increased risk of CVAs (RR = 1.845, 95% CI:1.049–3.244, p = 0.034). Carriers of the Lys751Gln genotype at the ERCC2 locus were at increased risk of CVAs (RR = 2.055, 95% CI:1.09–3.876, p = 0.025). Carriership of the E2/E3 genotype at the APOE locus decreased the risk of CVAs in Bulgarian males (RR = 0.279, 95% CI:0.090–0.873, p = 0.028). Male Bulgarian carriers of the APOE4 allele were at increased risk of CVAs. Carriership of the common prothrombotic mutations Factor V Leiden, PT G20210A, MTHFR C677T and PAI1 4G/5G had no significant effect on the risk of CVAs in Bulgarian adults.
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