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Title: GENDER DISPARITIES OF CIRCULATORY DISEASE PROGRESS IN THE CHORNOBYL ACCIDENT CLEAN-UP WORKERS AND PHOSPHODIESTERASE 4D GENE rs966221 POLYMORPHISM.
Author: Bilyi DO, Nastina OM, Sydorenko GV, Bilous NI, Kursina NV, Pleskach GV, Bazyka OD, Makarevysh OM, Kovaliov OS, Chumak AA, Abramenko IV.
Journal: Probl Radiac Med Radiobiol; 2018 Dec; 23():263-282. PubMed ID: 30582852.
Abstract:
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. Meta doslidzhennia: vyznachennia osoblyvosteĭ rozvytku gipertonichnoï khvoroby (GKh) ta ishemichnoï khvoroby sertsia(IKhS) v uchasnykiv likvidatsiï naslidkiv avariï (ULNA) na Chornobyl's'kiĭ AES (ChAES) i neoprominenykh osib zalezh-no vid stati ta genotypu polimorfizmu rs966221 gena fosfodiesterazy 4D (PDE4D).Materialy ta metody. Za period z 2013 po 2018 rr. obstezheno 515 cholovikiv-ULNA (ULNA-ch) i 145 zhinok-ULNA(ULNA-zh) 1986–1987 rr., a takozh 162 cholovikiv ta 120 zhinok kontrol'noï grupy (KG), iaki ne zaznaly radiatsiĭno-go vplyvu (vidpovidno KG-ch i KG-zh). U doslidzhennia vviĭshly osoby, iaki ne maly oznak GKh ta IKhS do avariï na ChAES.Rezul'taty. Analiz tablyts' vyzhyvannia za Kaplanom-Meĭierom pokazav, shcho za pokaznykom mediany vyzhyvanniaGKh rozvyvalas' v ULNA-ch ta ULNA-zh v bil'sh molodomu vitsi (47,5 -#177; 0,6) ta (50,7 -#177; 0,7) rokiv porivniano z KG-ch(54,9 -#177; 1,1 rokiv) ta KG-zh (54,4 -#177; 1,1 rokiv); te zh same stosuvalos' IKhS, de mediana dorivniuvala (56,8 -#177; 0,5),(61,2 -#177; 0,8), (61,6 -#177; 1,0) ta (64,2 -#177; 1,4) rokiv vidpovidno. Analiz nakopychenoï zakhvoriuvanosti na GKh ta IKhS ne vy-iavyv asotsiatsiï polimorfizmu rs966221 gena PDE4Dz tsymy zakhvoriuvanniamy. Nosiĭstvo genotypu TT v porivnianniz SS ta ST pidvyshchuvalo ryzyk rozvytku infarktu miokarda (IM) u 2,9 raza v ULNA-ch, u 4 razy v KG-ch ta u 5,5 raza –u KG-zh (r -#060; 0,05). V ULNA-zh nosiĭstvo bud'-iakogo genotypu ne asotsiiuvalo z IM. Nastannia menopauzy pryzvody-lo do pidvyshchennia zakhvoriuvanosti na GKh porivniano z cholovikamy.Vysnovky. Uchasnyky LNA na ChAES cholovichoï ta zhinochoï stati zaneduzhuvaly na GKh ta IKhS u bil'sh molodomu vitsiporivniano z vidpovidnym neoprominenym kontrolem. U cholovikiv-ULNA v porivnianni z zhinkamy-ULNA nakopyche-na chastota zakhvoriuvanosti na IM bula vyshcha u bud'-iakomu vikovomu diapazoni, na IKhS – z 23 do 74 rokiv, a na GKh –z 25 do 53 rokiv. U cholovikiv i zhinok, iak v ULNA, tak i v grupakh neoprominenogo kontroliu, GKh rozvynulasia znach-no ranishe IKhS. Nosiĭstvo genotypu TT polimorfizmu rs966221 gena PDE4Dzbil'shuie ryzyk rozvytku IM u cholovikiv-ULNA bud'-iakogo viku, a v neoprominenomu kontroli – z 65 rokiv u cholovikiv i z 60 rokiv u zhinok. Dlia zhinok-ULNAne otrymano danykh pro asotsiatsiiu genotypu danogo polimorfizmu z IM.

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