PROGNOSTIC ROLE OF A1166C POLYMORPHISMS OF THE ANGIOTENSINE II RECEPTOR GENE (AGT2R1) IN CORONARY ATHEROSCLEROSIS AMONG ADYGHEA REPUBLIC INHABITANTS

Aim. The investigation of A1166/166C polymorphisms of the vascular receptor 1 type of angiotensine II gene (AGT2R1) association with the development of coronary and peripheral atherosclerosis in ethnic groups ofAdygheaRepublicinhabitants.

Material and methods. The spread of A1166/166C polymorphic variants of the gene AGT2R1 was studied via the “single nucleotide polymorphism” (SNP) — method with allele-specific primers and electrophoretic results detection (by SPF “Litech”). Gene polymorphisms AGT2R1 (rs5186) with nucleotide replacement of adenine by cytosine (А>C) in the 1166th position of gene AGT2R1 were typified in the samples of donors genomic DNA (n=143) and of those with cardiovascular diseases (n=39) at the age 23-65 y. o. from two ethnic subgroups — Adyghes and Russians. The data was processed via software SPSS Statistics 17.0.

Results. In the group of those with complicated coronary and peripheral atherosclerosis there was statistically significant increase of the prevalence of mutant1166Callele and of pathological monozygous genotype C1166C. The risk of cardiovascular diseases in the carriers of1166Callele increases 3,77 times (c2 =26,07; р=0,00003), and in the case with homozygous “mutant” CC genotype — 10,36 times (c2 =31,20; р=0,00002), that makes it to use the1166Callele and С1166С genotype AGT2R1 as genetic predictors of coronary atherosclerosis and markers of prenosological diagnostics of ischemic heart disease (c2 =42,96; р=0,0000005; OR (95%)=17,37).

Conclusion. The results of this study, together with additional instrumental investigations of cardiovascular system functioning will help to improve the precision of diagnostics of atherosclerosis and its possible complications at earlier stages, that will help to decrease disability rate and mortality in economically active citizens. 

1. Puzyrev VP, et al. Genes sintropy and cardiovascular continuum. Bulletin VOGiS 2006; 3: 479-93. Russian (В. П. Пузырев и др. Гены синтропий и сердечно-сосудистый континуум. Вестник ВОГиС 2006; 3: 479-93).

2. Roytberg GE, Strutynsky AV. Internal diseases. Cardiovascular system. М: BINOM; 2003. Russian (Г. Е. Ройтберг, А. В. Струтынский. Внутренние болезни. Сердечнососудистая система. М: БИНОМ; 2003).

3. HuGENavigator (электронный ресурс) — Режим доступа — http:// www.hugenavigator. net/HuGENavigator.

4. Furuta О, et al. Molecular cloning, sequence analysis and expression of a cDNA encoding human type-1 angiotensin II receptor. Biochem. Biophys. Res. Commun 1992; 183: 910-16.

5. Muzhenya DV, Tuguz AR, et al. Association Met235 Thr polymorphism of angiotensinogen (AGT) and A1166C allele receptor type I angiotensinogen-2 (AGT2R1) with cardiovascular disease (CVD) among residents of the Republic of Adygea. Bulletin of AGU. Ser. natural and mathematical sciences and engineering 2010; 62: 102-11. Russian (Д. В. Муженя, А. Р. Тугуз и др. Ассоциация Met235 Thr полиморфизма гена ангиотензиногена (AGT) и A1166C аллели рецептора I типа ангиотензиногена-2 (AGT2R1) с сердечно-сосудистыми заболеваниями (ССЗ) у жителей Республики Адыгея. Вестник АГУ. Сер. естественно-математических и технических наук 2010; 62: 102-11).

6. Muzhenya DV, Tuguz AR, Anokhina EN, et al. A new approach to the diagnosis of preclinical cardiovascular disease in elite athletes of the Republic of Adygea. Theory and Practice of Physical Culture 2013; 8: 30-3. Russian (Д. В. Муженя, А. Р. Тугуз, Е. Н. Анохина и др. Новый подход к донозологической диагностике сердечно-сосудистых заболеваний у высококвалифицированных спортсменов Республики Адыгея. Теория и практика физической культуры 2013; 8: 30-3).

7. OMIM. URL: http:// omim.org.

8. The Allele Frequency Database. URL: http://alfred.med.yale.edu.

9. Zateyshchikov DA. The study of anticoagulant properties of the endothelium with a standard venoocclusive test. Bulletin of Experimental Biology and Medicine 2007; 12: 605-8. Russian (Д. А. Затейщиков. Изучение антикоагулянтных свойств эндотелия с помощью стандартного веноокклюзивного теста. Бюллетень экспериментальной биологии и медицины 2007; 12: 605-8).

10. Tseluyko VI, Popova EI. Genetic aspects of a myocardial infarction. Heart і sudini 2008; 1: 47-53. Russian (В. И. Целуйко, Е. И. Попова. Генетические аспекты инфаркта миокарда. Серце і судини 2008; 1: 47-53). 11. Dyatlova AM. Results of a tipirovaniye of a gene of a receptor of 1 type of angiotensin 2 A1166C among the men of working-age who had a myocardial infarction in Republic of Belarus. Collection of materials II of the Youth innovative forum. Minsk 2012: 95-8. Russian (А. М. Дятлова, Результаты типирования гена рецептора 1 типа ангиотензина 2 А1166С среди мужчин трудоспособного возраста, перенесших инфаркт миокарда в Республике Беларусь. Сборник материалов II Молодежного инновационного форума. Минск 2012: 95-8).

11. Kalakutok ZN. Gene polymorphism of the renin-angiotensin-aldosterone system and the risk of developing essential hypertension in Circassians and Russian 1998-2002gg.: Author ref. candidate of medical sciences. Chelyabinsk, 2002. 24р. Russian (З. Н. Калакуток. Полиморфизм генов ренин-ангиотензин-альдостероновой системы и риск развития эссенциальной гипертонии у адыгов и русских: 1998-2002гг.: Автореф. дис. канд. мед. наук. Челябинск, 2002. 24с).

12. Su SL, Yang HY, Wu CC, et al. Gene-gene interactions in renin-angiotensin-aldosterone system contributes to end-stage renal disease susceptibility in a Han Chinese population. Scientific World Journal 2014; 10: 352-8.

13. Jin Y, Kuznetsova T, Thijs L, et al. Association of left ventricular mass with the AGTR1 A1166C polymorphism. Am. J. Hypertens. 2012; 4: 472-8.

14. Li Y, et al. Meta-analysis of the association between angiotensin II receptor, type 1 gene A1166C polymorphism and coronary artery disease in Chinese populations. J. Renin Angiotensin Aldosterone Syst. 2013; 14: 82-90.