Pleskach G. Impact of SNP83 polymorphism of phosphodiesterase 4D gene in genetic predisposition to myocardial infarction development in sufferers of Chornobyl NPP accident

Thesis for the acquisition of candidate's degree in speciality 03.00.01 - radiobiology (medical sciences). - SI "National Research Center for Radiation Medicine, National Academy of Medical Sciences of Ukraine", Kyiv, 2014. The thesis is devoted to the study of modified influence of ionizing radiation on realization of genetic predisposition (SNP83 polymorphism of PDE4D gene) to myocardial infarction development in sufferers of Chornobyl NPP accident. The investigation of SNP83 (rs966221) PDE4D gene polymorphism was conducted in the main group of sufferers due to Chornobyl NPP accident (259 patients) and in the control group (187 patients). Men of the control group, carriers of TT genotype, had increased risk of myocardial infarction (MI) development at the age of >60 years (Odds ratio, OR = 9.2; 95% confidence interval 1.11-15.96; p=0.016) and increased number of traditional risk factors. On the contrary, men of the main group, carriers of TT genotype, had increased MI risk (OR = 2.44; 95% confidence interval 1.22-4.894; p=0.01) in spite of age at MI development. Moreover, absorbed dose of irradiation in clean-up workers who developed MI at the age under 60 years was higher comparing with clean-up workers who developed MI at the age over 60 years (34.10 ± 10.44 sSv and 10.42 ± 3.12 sSv, correspondingly, р=0.039). TT genotype carriers developed MI at a younger age compared with carriers of other genotypes (p=0.031). There was an inverse correlation between the dose of irradiation and the age of MI development (r=-0.588; p=0.001), which was statistically significant only in carriers of the T allele of PDE4D gene. It may be suggested that genetic predisposition (TT genotype of rs966221 PDE4D gene polymorphism) led to development of endothelial dysfunction, expecially under action of ionizing radiation, and increased MI risk. Key words: ionizing radiation, clean-up workers of Chornobyl NPP accident, myocardial infarction, rs966221 phosphodiesterase 4D gene (PDE4D) polymorphism