MOLECULAR GENETIC ASPECTS OF THE RISK FOR FAMILY ADENOMATOUS POLYPOSIS

DOI: https://doi.org/10.29296/24999490-2018-06-11

T.A. Muzaffarova(1), D.J. Mansorunov(1), I.Y. Sachkov(2), A.Y. Kuzevanova(1), A.V. Karpukhin(1), A.A. Alimov(1) 1-Research Center for Medical Genetics, Moskvorechye str., 1, Moscow, 115478, Russian Federation; 2-Bakhrushins brothers Municipal clinical hospital, Stromynka str., 7, Moscow, 115478, Russian Federation Е-mail: [email protected]

Introduction. The origin of the genetic predisposition to family adenomatous polyposis is associated with functional disorders of the repair system. The molecular mechanism of this phenomenon is not sufficiently studied and need clarification. The aim of the study. To evaluate the relation of rs2155209 MRE11А gene polymorphism with the disease in patients who are or are not carriers of mutations in APC and MUTYH genes. Methods. The study was carried out by conventional methods for DNA polymorphism and mutations detection including conformation sensitive gel electrophoresis and DNA sequencing. Statistical evaluation of the data was performed using Microsoft Excel and MEDCALC software. Results. The association of rs2155209 polymorphism with the disease prevalence was evaluated. The spectrum of APC gene mutations was determined on the patient sample with adenomatous polyposis. Microdeletions of the APC gene were shown to be the most common event and compose about half of the mutations in our sample. New mutations of this gene were revealed in ten families. No mutations in APC and MUTYH genes was observed in 39% of cases. The association of MRE11А gene, locus rs2155209, allele «C» with polyposis in the sample without mutations was shown. The allele «C» is one of the risk factors of polyposis in the sample of patients without mutations (OR=2,8; 95% CI: 1,42–5,53; p=0,0029). Allele «C» is not a risk modifier in the presence of mutations in АРС gene. On the other hand, the TT genotype is associated with a reduced risk of adenomatous polyposis without mutations in the APC gene. Conclusion. Changes in the level of MRE11А gene expression could be assumed occurring due to the polymorphism that may have significance for polyposis formation.
Keywords: 
germinal mutations, family adenomatous polyposis, microdeletions, polymorphism, disease
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