GENDER DISPARITIES OF CIRCULATORY DISEASE PROGRESS IN THE CHORNOBYL ACCIDENT CLEAN-UP WORKERS AND PHOSPHODIESTERASE 4D GENE rs966221 POLYMORPHISM. / GENDERNI VIDMINNOSTI ROZVYTKU ZAKhVORIuVAN' SYSTEMY KROVOOBIGU V UChASNYKIV LIKVIDATsIÏ NASLIDKIV ChORNOBYL'S'KOÏ AVARIÏ I POLIMORFIZM rs966221 GENA FOSFODIESTERAZY 4D.

OBJECTIVE: Evaluation of the hypertensive disease (HD) and coronary heart disease (CHD) progress in the ChornobylNPP (ChNPP) accident clean-up workers (ACUW) and persons not exposed to ionizing radiation depending on gen-der and genotype of the phosphodiesterase 4D (PDE4D) gene rs966221 polymorphism. MATERIALS AND METHODS: There were male ACUW (ACUWm; n=515) and female ACUW (ACUWf; n=145) involved in thestudy since 2013 till 2018. Participation in the clean-up works took place in 1986-1987. The control group includ-ed male (CGm; n=162) and female (CGf; n=120) persons not exposed to ionizing radiation. All study subjects havehad neither signs nor symptoms of HD or CHD before the ChNPP accident. RESULTS: Review of the Kaplan-Meier survival tables indicated that according to median survival the HD emerged inACUWm and ACUWf in a younger age (47.5 ± 0.6 and 50.7 ± 0.7 years old, respectively) vs. CGm or CGf (54.9 ± 1.1 and54.4 ± 1.1 years, respectively). The same was true for CHD where the median values were (56.8 ± 0.5), (61.2 ± 0.8),(61.6 ± 1.0) and (64.2 ± 1.4) years respectively. Review of cumulative incidence of HD and CHD revealed no associ-ation of the PDE4D gene rs966221 polymorphism with the diseases of concern. The TT gene carrier state comparedto the CC or CT genes features an increased risk of myocardial infarction (MI) 2.9 times in ACUWm, 4-fold in CGm, and5.5 times in CGf (p < 0.05). No any gene carrier state was associated with MI in the ACUWf. Onset of menopause wasfollowed by an increase in HD incidence vs. males. CONCLUSIONS: The male and female ChNPP ACUW were developing HD and CAD at a younger age compared with cor-responding non-irradiated control. In male ACUW in comparison with female ACUW the cumulative morbidity ratefor MI was higher in any age range, whereas for CAD it was higher from 23 to 74 years, and for HD from 25 to 53 yearsof age. In male and female ACUW as well as in non-irradiated control the HD developed much earlier than CHD. Thecarrier state of TT genotype of PDE4D gene rs966221 polymorphism increases the risk of MI in males of all ages, inthe non-irradiated controls it is increased in 65 years for men and in 60 years for women. No data on association ofthe genotype of the described gene polymorphism with MI were found in female ACUW.

Features of coronary heart disease development in emergency workers of the Chornobyl accident depending on the action of radiation and non radiation risk factors and genotypes of single nucleotide polymorphism rs966221 of phosphodiesterase 4D gene. / OSOBLYVOSTI ROZVYTKU IShEMIChNOÏ KhVOROBY SERTsIa V UChASNYKIV LIKVIDATsIÏ NASLIDKIV ChORNOBYL'S'KOÏ AVARIÏ V ZALEZhNOSTI VID DIÏ RADIATsIY̆NYKh I NERADIATsIY̆NYKh FAKTORIV RYZYKU TA NOSIY̆STVA GENOTYPIV ZA POLIMORFIZMOM RS966221 GENU FOSFODIESTERAZY 4D.

OBJECTIVE: This study devoted to specific features of coronary heart disease (CHD) development in emergency work ers (EW) of the accident at the Chernobyl nuclear power plant (ChNPP) based on analysis the interaction between radiation and non radiation risk factors and single nucleotide polymorphism (SNP) rs966221 of phosphodiesterase (PDE) 4D gene. METHODS: It was examined 397 men with CHD, including 274 EW of 1986-1987 and 123 non irradiated persons (con trol group) who were 66±10 and 69±11 years old relatively. The program studies included clinical examination, elec trocardiography (ECG), ECG daily monitoring, ECG stress testing, echo doppler cardiography, analysis of serum lipid spectrum, polymerase chain reaction with restriction of reaction products, retrospective analysis of case histories. Diagnosis of CHD or its approval was carried out in accordance with the standards of diagnosis, accepted in Ukraine. All EW before their taking part in cleaning ChNPP territory did not suffered from CHD. RESULTS: According to the analysis of contingency tables, carriers of the TT genotype of rs966221 increased the risk of myocardial infarction (MI) in 2.538 times compared with carriers of genotypes CC and CT. The use of Kaplan Meier method showed that a half of EW with the TT genotype developed MI before 64 years old, while with the other geno types up to 78.7 years old. In the control group statistically significant increase of cumulative proportion of patients with MI, carriers of the TT genotype, began from 60 years old. Compared to the non irradiated patients EW fell ill with CHD on 9.4 years earlier. Using proportional hazards analysis (Cox regression), it was found that EW had 3.9 times higher risk of CHD than in non irradiated individuals. Smoking and overweight brought three times less but significant risk - 1.37 and 1.33 respectively. The TT genotype unlike genotypes CC and CT gene PDE4D increased risk of MI in 1.757 times more both in EW and control group. CONCLUSIONS: The risk of CHD development was determined by radiation factor, such as the involvement in the emer gency works of the accident consequences, as well as non radiation factors, namely smoking and overweight. Only one factor, the TT genotype of rs966221 PDE4D gene, determined the risk of MI occurrence in EW and non irradiated controls. In the post emergency period, CHD developed 6 years earlier in EW with the TT genotype than in patients with genotypes CC and CT.

Structural and functional state of heart left ventricle depending on polymorphism rs966221 phosphodiesterase 4D gene in emergency workers of the Chornobyl NPP suffering from coronary heart disease. / STRUKTURNO FUNKTsIONAL'NYY̆ STAN MIOKARDA LIVOGO ShLUNOChKA SERTsIa V UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChORNOBYL'S'KIY̆ AES Z IShEMIChNOIu KhVOROBOIu SERTsIa ZALEZhNO VID POLIMORFIZMU rs966221 GENA FOSFODIESTERAZY 4D.

OBJECTIVE: This study consisted in examination the features of structural and functional state of the cardiovascular system in emergency workers (EW) of the Chernobyl nuclear power plant (ChNPP) who suffered from coronary heart disease (CHD) and having different genotypes due to polymorphism rs966221 phosphodiesterase 4D (PDE4D) gene. MATERIALS AND METHODS: The study involved 121 EW and 63 non irradiated patients with CHD. Standardized survey included echo doppler cardiography (EchoCG) that was done by Diagnostic Ultrasound System DS N3 (Mindray). Polymorphism rs966221 PDE4D determined by polymerase chain reaction followed by restriction reaction products. RESULTS: The distribution of genotypes PDE4D in EW was as follows: CC - 42, CT - 49 and TT - 30 patients. In the con trol group, carriers of the same genotypes were 27, 21 and 15 persons respectively. All echocardiographic parame ters in EW workers and non irradiated patients did not differ significantly. Amongst TT genotype carriers of both groups the proportion of patients with increased myocardial mass index was the highest (82.9%) compared to CC genotype (78.4%) and CT (71.4%). The concentric type of left ventricular (LV) hypertrophy was found in 54.9% of patients with CC genotype, in 51.8% with CT genotype and 45.7% with TT genotype, while the eccentric type in 23.5, 21.4 and 37.1% respectively. The relative number of people with high LV end diastolic volume (EDV) normalized by body surface area (BSA) was 27.5% in CC genotype carriers, 26.8% in CT genotype and 40% in TT genotype carriers (p > 0.05). The increase of BSA indexed LV end systolic volume (ESV) was found in 27.5, 30.4 and 28.6%, and the ejection fraction in 15.7, 23.2 and 22.9% respectively. The largest number of CHD patients with inadequate dias tolic function was in carriers of TT genotype (75%) compared with the data in CC (66.7%) and CT genotypes (42.9%) carriers. CONCLUSIONS: In patients with the same genotype, both EW and non irradiated persons there were virtually no dif ferences in indicators of the structural and functional status of LV. The analysis of changes of LV structure the fol lowing feature was revealed: eccentric type of LV hypertrophy was more common for patients with TT genotype, but concentric type for CC genotype carriers. In one third of patients with CC and CT genotypes and in 40% of TT geno type carriers it was observed LV systolic function disorders. Diastolic dysfunction manifested as often in patients with TT genotype compared with CC and CT genotypes carriers.

Analysis of some risk factors for myocardial infarction in a cohort of the Chornobyl clean-up workers (according to the data of Clinical and Epidemiological Registry).

UNLABELLED: The objective of the paper was to analyze the individual risk factors for coronary heart disease in a group of clean-up workers, who had developed a myocardial infarction (MI) after the Chornobyl NPP accident. METHODS: Data of 525 clean-up workers with a first MI event were analyzed among all uniquely identifiable clean-up workers registered in the Clinical and Epidemiological Registry (CER) of NRCRM. The comparison was carried out with a control group of 110 residents of Kyiv, who had MI within 2004-2009. RESULTS: It was found that the proportion of patients who had MI under 45 years was increased in the first 10 years after the Chornobyl accident, being first of all due to the age structure of the clean-up worker's cohort as a whole. The distribution of patients by age in the following years was close to that in the other MI cohorts described in the literature. The external radiation dose of men who developed MI in the first 5 years after the Chornobyl NPP accident was 39.58 ± 6.72 cSv (median 25 cSv) which exceeded the dose of men who had got the MI later (23.78 ± 2.43 cSv, median 12 cSv; p=0.009). CONCLUSIONS: The quantity of the male patients with minimum number of risk factors was gradually reducing along with time since the Chornobyl accident and accordingly the proportion of patients with three or more risk factors was increased (p=0.001). Incidence of obesity and hypercholesterolemia among male clean-up workers was higher than in the control group of male inhabitants of Kyiv.