rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.47360/1995-4484-2022-64-71rsp-3118Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHУчастие полиморфизмов генов TNF, CRP и SAA1 в формировании предрасположенности к развитию анкилозирующего спондилита и его клинических проявленийInvolvement of polymorphisms of TNF, CRP and SAA1 genes in the predisposition to the development of ankylosing spondylitis and its clinical manifestationshttps://orcid.org/0000-0002-9922-5124КрыловМ. Ю.KrylovM. Yu.

Крылов Михаил Юрьевич

115522, Москва, Каширское шоссе, 34а

Mikhail Krylov

115522, Moscow, Kashirskoye Highway, 34A

mekry@yandex.ruhttps://orcid.org/0000-0002-4906-7148ГусеваИ. А.GusevaI. A.

115522, Москва, Каширское шоссе, 34а

Irina A. Guseva

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0003-2486-8798СахароваК. В.SakharovaK. V.

115522, Москва, Каширское шоссе, 34а

Ksenia V. Sakharova

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0001-7501-9185СамаркинаЕ. Ю.SamarkinaE. Yu.

115522, Москва, Каширское шоссе, 34а

Elena Yu. Samarkina

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0003-3195-5187ЭрдесШ. Ф.ErdesS. F.

115522, Москва, Каширское шоссе, 34а

Shandor F. Erdes

115522, Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0003-4316-1077КоноваловаН. В.KonovalovaN. V.

127550, Москва, ул. Тимирязевская, 42

Nina V. Konovalova

127550,Moscow, Timiryazevskaya str., 42

https://orcid.org/0000-0001-7004-981XВарламовД. А.VarlamovD. A.

127550, Москва, ул. Тимирязевская, 42

Dmitry A. Varlamov

127550,Moscow, Timiryazevskaya str., 42

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian FederationФГБНУ «Всероссийский научно-исследовательский институт сельскохозяйственной биотехнологии»РоссияAll-Russian Research Institute of Agricultural BiotechnologyRussian Federation20222802202260164–71Copyright © Крылов М.Ю., Гусева И.А., Сахарова К.В., Самаркина Е.Ю., Эрдес Ш.Ф., Коновалова Н.В., Варламов Д.А., 20222022Крылов М.Ю., Гусева И.А., Сахарова К.В., Самаркина Е.Ю., Эрдес Ш.Ф., Коновалова Н.В., Варламов Д.А.Krylov M.Y., Guseva I.A., Sakharova K.V., Samarkina E.Y., Erdes S.F., Konovalova N.V., Varlamov D.A.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/3118

Цель исследования – изучить участие полиморфизмов генов TNF (-308G/A, rs1800629), CRP (+1846C/T, rs1205) и SAA1 (-13T/C, rs12218) в формировании предрасположенности к развитию анкилозирующего спондилита (АС) и клинических фенотипов АС.Материалы и методы. В исследование были включены 122 пациента с диагнозом АС, соответствующим модифицированным Нью-Йоркским критериям. 109 (89,3%) из них были позитивны по HLA-B*27. Периферический артрит выявлен у 71 (58,2%), энтезиты – у 92 (75,4%), коксит – у 82 (67,2%) больных. Все пациенты имели высокую степень активности по BASDAI, который в среднем составлял 5,6±1,2. В контроль ную группу вошли 142 практически здоровых донора крови. Полиморфизмы были изучены с помощью аллель-специфической полимеразной цепной реакции в реальном времени.Результаты. Обнаружены статистически значимые различия по частоте генотипов и аллелей полиморфизма -308G/A гена TNF а также аллелей полиморфизма -13T/C гена SAA1 между пациентами и контрольной группой (p=0,01, p=0,01 и p=0,03 соответственно). Логистический регрессионный анализ показал, что присутствие не менее одного аллеля -308A в генотипе пациента снижало риск развития АС в 4,4 раза по сравнению с генотипом GG (р=0,01). У носителей генотипа GA вероятность предрасположенности к развитию энтезитов была в 2,2 раза ниже по сравнению с носителями генотипа GG (р=0,01). Установлена связь полиморфизма +1846C/T гена CRP с предрасположенностью к периферическому артриту. Носительство аллеля T в 2 раза повышало предрасположенность к артриту по сравнению с аллелем С (р=0,02). Носительство не менее одного аллеля rs12218 С гена SAA1 в 2 раза повышало предрасположенность к АС (р=0,01).Заключение. Полученные данные подтверждают участие полиморфизмов генов TNF (-308G/A, rs1800629), CRP (+1846C/T, rs1205) и SAA1 (-13T/C, rs12218) в формировании предрасположенности к развитию АС. Полиморфизм гена TNF ассоциирован с возникновением энтезитов, а полиморфизм гена CRP – с предрасположенностью к периферическому артриту

Objective. To study the involvement of the rs1800629 G/A polymorphisms of the TNF-α gene, rs1205C/T of the CRP gene, and rs12218T/C of the SAA1 gene in the predisposition to ankylosing spondylitis (AS) and their role in the formation of clinical phenotypes of AS.Materials and methods. 122 patients with AS were included in the study. All patients had a diagnosis of AS based on the modified New York criteria. The presence of the HLA-B27 antigen was detected in 109 (89.3%) patients, the presence of peripheral arthritis – in 71 (58.2%), enthesitis – in 92 (75.4%), coxitis – in 82 (67.2%) patients. All patients had a high degree of activity with an average BASDAI index of 5.6±1.2. The control group consisted of 142 healthy blood donors. Polymorphisms were studied using allele-specific real-time polymerase chain reaction (RT-PCR).Results. Significant differences were found in the frequencies of genotypes and alleles of the -308G/A polymorphism of the TNF gene and the frequencies of alleles of the rs12218 T/C polymorphism of the SAA1 gene between patients and the control group (p=0.01, p=0.01 and p=0.03 respectively). Logistic regression analysis showed that the presence of at least one -308A allele in the patient’s genotype reduced the risk of developing AS by 4.4 times compared with the GG genotype (p=0.006). In carriers of the GA genotype, the probability of a predisposition to the development of enthesitis was 2.2 times lower than in carriers of the GG genotype (p=0.01). The relationship between the rs1205 polymorphism of the CRP gene and the predisposition to peripheral arthritis has been established. Carriage of the rs1205T allele doubled the susceptibility to arthritis compared with the rs1205C allele (p=0.013). Carriage of at least one rs12218C allele of the SAA1 gene doubled the susceptibility to AS (p=0.018).Conclusion. The data obtained confirm the involvement of polymorphisms rs1800629 of the TNF gene, rs1205 of the CRP gene, and rs12218 of the SAA1 gene in the predisposition to AS. TNF gene polymorphism is associated with the formation of the clinical phenotype of enthesitis, and CRP gene polymorphism is associated with a predisposition to peripheral arthritis.

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