rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2018-55-59rsp-2500Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHПолиморфизм генов эндотелиальной дисфункции, коактиваторов митохондриального биогенеза и плазминоген-плазминовой системы в развитии кардиоваскулярных осложнений при ревматоидном артритеGENE POLYMORPHISMS OF ENDOTHELIAL DYSFUNCTION, COACTIVATORS OF MITOCHONDRIAL BIOGENESIS AND PLASMINOGEN/PLASMIN SYSTEM IN THE DEVELOPMENT OF CARDIOVASCULAR EVENTS IN RHEUMATOID ARTHRITISШевченкоА. В.ShevchenkoA. V.

Новосибирск.

Novosibirsk.

shalla64@mail.ruПрокофьевВ. Ф.ProkofyevV. F.

Новосибирск.

Novosibirsk.

КоролевМ. А.KorolevM. O.

Новосибирск.

Novosibirsk.

ОмельченкоВ. О.OmelchenkoV. O.

Новосибирск.

Novosibirsk.

КоненковВ. И.KonenkovV. I.

Новосибирск.

Novosibirsk.

ФГБНУ «Научноисследовательский институт клинической и экспериментальной лимфологии».РоссияResearch Institute of Clinical and Experimental Lymphology.Russian FederationФГБНУ «Научноисследовательский институт клинической и экспериментальной лимфологии» .РоссияResearch Institute of Clinical and Experimental Lymphology.Russian Federation2018030320185615559Copyright © Шевченко А.В., Прокофьев В.Ф., Королев М.А., Омельченко В.О., Коненков В.И., 20182018Шевченко А.В., Прокофьев В.Ф., Королев М.А., Омельченко В.О., Коненков В.И.Shevchenko A.V., Prokofyev V.F., Korolev M.O., Omelchenko V.O., Konenkov V.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/2500

Наиболее частой причиной смерти у пациентов с ревматоидным артритом (РА) являются сердечно-сосудистые катастрофы. При этом механизм прогрессирования атеросклеротического поражения сосудистого русла при РА, включая генетические факторы, остается предметом дискуссий.

Цель исследования – анализ ассоциированности полиморфизма генов NOS3, PPARG γ , PPARGC1А, PPARGC1B и PAI1 с наличием высокого/низкого сердечно-сосудистого риска у пациентов с РА.

Материал и методы

Материал и методы. В исследование включены 73 пациента с РА. Высокий риск развития сердечно-сосудистых осложнений имели 67,1% из них. В качестве суррогатного маркера кардиоваскулярного риска использовалось ультразвуковое исследование брахиоцефальных артерий с определением толщины комплекса интима–медиа (ТКИМ). Сравнение проводилось с учетом соответствующих норм. Значение ТКИМ, превышающее указанные показатели, расценивалось как признак высокого кардиоваскулярного риска. Однонуклеотидный полиморфизм генов NOS3 (rs2070744), PPARG2 (rs1801282), PPARGC1A (rs8192678), PPARGC1B (rs7732671), PAI1 (rs1799889) исследовали с помощью полимеразной цепной реакции в режиме реального времени с использованием интеркалирующего красителя SYBR Green I согласно инструкции фирмы-производителя («Литех», Россия).

Результаты и обсуждение

Результаты и обсуждение. Частоты генотипов NOS3 -786TТ значимо различались у пациентов с разным риском развития сердечно-сосудистых осложнений. Выявлены сложные генотипы, частота которых превалирует в группе с низким риском развития сердечно-сосудистых событий. При этом в составе всех генотипов присутствует гомозиготный генотип NOS3 -786TТ и гены, обладающие способностью регулировать его экспрессию. Наибольшие различия между анализируемыми группами представлены в комплексах NOS3-786 TT:PPARGC1B 203AlaAla и NOS3 -786TT:PPARGC1B 203AlaAla:PPARG 12 ProPro.

Выводы

Выводы. Проанализированные нами полиморфные позиции генов сочетанно могут оказывать влияние на риск сердечно-сосудистых осложнений у пациентов с РА.

Cardiovascular catastrophes are the most common cause of death in patients with rheumatoid arthritis (RA). At the same time, the mechanism of progression of atherosclerotic lesions in the vascular bed in RA, including genetic factors, remains a matter of debate.

Objective

Objective: to analyze the associativity of polymorphism of the NOS3, PPARG γ , PPARGC1А, PPARGC1B and PAI-1 gene with a high/low cardiovascular risk in patients with RA.

Subjects and methods

Subjects and methods. The investigation enrolled 73 patients with RA. Of them, 67.1% were at high cardiovascular risk. Ultrasonography of the brachiocephalic arteries with determination of intima-media thickness (IMT) was used as a surrogate marker for cardiovascular risk. A comparison was carried out taking into account the relevant standards. The IMT value exceeding the above parameters was regarded as the sign of a high cardiovascular risk. Single nucleotide polymorphisms in the NOS3 (rs2070744), PPARG2 (rs1801282), and PPARGC1A (rs8192678), PPARGC1B (rs7732671), and PAI1 (rs1799889) genes were investigated by a real-time polymerase chain reaction assay using the intercalating dye SYBR Green I according to the instructions of the manufacturer («Litech», Russia).

Results and discussion

Results and discussion. The frequencies of the NOS3 -786ТТ genotypes significantly differed in patients at different cardiovascular risks. Complex genotypes, the frequency of which was prevalent in the low cardiovascular risk group, were identified. At the same time, all genotypes contained the homozygous NOS3 -786ТТ genotype and the genes that were able to regulate its expression. The greatest differences between the analyzed groups were present in the complexes of NOS3-786TT:PPARGC1B 203AlaAla and NOS3 -786TT:PPARGC1B 203AlaAla:12 PPARG ProPro.

Conclusion

Conclusion. Our analyzed gene polymorphic positions can concurrently affect cardiovascular risk in patients with RA. 

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The authors declare that there are no conflicts of interest present.