INDIVIDUAL CAPACITY FOR MAINTENANCE OF GENOMIC INTEGRITY - A NOVEL TOOL IN THE ASSESSMENT OF THE RISK FOR COMMON ADULT-ONSET HUMAN DISEASES AND CONDITIONS AND THEIR LATE COMPLICATIONS
CHELENKOVA P.1, PETKOVA R.1, CHAKAROV S.2*
1 – Scientific Technological Service (STS), Ltd., Sofia, Bulgaria
2 – Sofia University ‘St. Kliment Ohridsky’, Sofia, Bulgaria
*Corresponding author: stoianchakarov@gmail.com
Keywords: individual capacity for management of genomic integrity, DNA repair, genetic markers, risk assessment
Abstract: Not until long ago, common diseases and disease-associated conditions with onset in adult life (obesity; insulin resistance; diabetes type 2; atherosclerosis; vascular disease; degenerative joint disease; neurological diseases; some types of cancer, and others) were considered to be a cumulative product of multiple lifestyle choices, despite the ample evidence that late-onset diseases tend to run in families. It is known now that genetic predisposition plays a significant role in the risk for development of adult-onset disease, albeit some environmental factors (e.g. diet and exercise, exposure to tobacco smoke, UV irradiation, and others) may increase or decrease the risks conferred by the genetic background. This study analyses the major effects of the carriership of common genetic polymorphisms in genes coding for proteins functioning in damage-associated signalling detection and maintenance of genomic integrity (TP53 P72R, XPC ins83); specific DNA repair pathways such as NER (XPC ins83, ERCC1 C8092A; XPD Lys751Gln), BER (XRCC1 Arg399Gln), strand break repair (XPCC1 Arg399Gln; XRCC3 Thr241Met) and disordered DNA methylation (MTHFR C677T) in clinically healthy individuals and in patients affected with specific diseases with late onset. Preliminary studies of the normal variance of these polymorphisms may be useful in establishment of a basis for more accurate risk assessment and individualization of therapies for common late-onset diseases and conditions.