mrjСовременная ревматологияModern Rheumatology Journal1996-70122310-158XIMA-PRESS, LLC10.14412/1996-7012-2023-5-29-35mrj-1473Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL INVESTIGATIONSВзаимосвязь полиморфизмов генов IRF5 (rs2004640), STAT4 (rs7574865) и TNFAIP3 (rs6920220, rs2230926) с синдромом Шегрена и его осложнением – MALT-лимфомойAssociation of IRF5 (rs2004640), STAT4 (rs7574865), and TNFAIP3 (rs6920220, rs2230926) gene polymorphisms with primary Sjögren's syndrome and its complication, MALT-lymphomahttps://orcid.org/0000-0002-4906-7148ГусеваИ. А.GusevaI. A.

Ирина Анатольевна Гусева

115522

Каширское шоссе, 34А

Москва

Irina Anatolievna Guseva

115522

Moscow

irrgus@yandex.ruhttps://orcid.org/0000-0001-8099-2107ТоргашинаА. В.TorgashinaA. V.

115522

Каширское шоссе, 34А

Москва

115522

34A, Kashirskoye Shosse

Moscow

https://orcid.org/0000-0003-2314-1466ХванЮ. И.KhvanJ. I.

115522

Каширское шоссе, 34А

Москва

115522

34A, Kashirskoye Shosse

Moscow

https://orcid.org/0000-0002-9922-5124КрыловМ. Ю.KrylovM. Yu.

115522

Каширское шоссе, 34А

Москва

115522

34A, Kashirskoye Shosse

Moscow

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

115522

Каширское шоссе, 34А

Москва

115522

34A, Kashirskoye Shosse

Moscow

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

127550

Тимирязевская ул., 42

Москва

127550

42, Timiryazevskaya Street

Moscow

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

127550

Тимирязевская ул., 42

Москва

127550

42, Timiryazevskaya Street

Moscow

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian FederationФГБНУ «Всероссийский научно-исследовательский институт сельскохозяйственной биотехнологии»РоссияRussian Research Institute of Agricultural BiotechnologyRussian Federation2023161020231752935Copyright © Гусева И.А., Торгашина А.В., Хван Ю.И., Крылов М.Ю., Самаркина Е.Ю., Коновалова Н.В., Варламов Д.А., 20232023Гусева И.А., Торгашина А.В., Хван Ю.И., Крылов М.Ю., Самаркина Е.Ю., Коновалова Н.В., Варламов Д.А.Guseva I.A., Torgashina A.V., Khvan J.I., Krylov M.Y., Samarkina E.Y., 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://mrj.ima-press.net/mrj/article/view/1473

   Появляется все больше данных, подтверждающих вклад не-HLA-генетических маркеров в предрасположенность к развитию синдрома Шегрена (СШ) и его тяжелого осложнения – MALT-лимфомы.

   Цель исследования – изучить ассоциацию полиморфизмов генов IRF5 (rs2004640), STAT4 (rs7574865) и TNFAIP3 (rs6920220, rs2230926) с предрасположенностью к развитию СШ и MALT-лимфомы.

   Материал и методы

   Материал и методы. В исследование включено 80 больных СШ (основная группа) и 103 индивида без аутоиммунной патологии (контрольная группа), сопоставимых по полу и возрасту с больными основной группы. У 16 пациентов была выявлена MALT-лимфома. Генотипирование полиморфизмов генов IRF5 (rs2004640), STAT4 (rs7574865), TNFAIP3 (rs6920220, rs2230926) выполнено методом полимеразной цепной реакции в режиме реального времени с использованием оригинальных аллель-специфических зондов, меченных различными флюоресцентными метками.

   Результаты и обсуждение. Распределение генотипов и аллелей гена STAT4 статистически значимо различалось в основной и контрольной группах (р = 0,0005 и р = 0,0001 соответственно). Наличие гомозиготного генотипа ТТ повышало риск развития СШ более чем в 8 раз по сравнению с генотипами TG+GG (отношение шансов, ОШ 8,2; 95 % доверительный интервал, ДИ 2,5–30,0; р = 0,0001). Полиморфизм гена TNFAIP3 rs2230926 также был ассоциирован с риском развития СШ: наличие генотипа TG значимо повышало вероятность возникновения СШ по сравнению с генотипом TT (ОШ 6,4; 95 % ДИ 1,2–44,3; р = 0,01). Наличие MALT-лимфомы было ассоциировано с полиморфизмом rs6920220 гена TNFAIP3. У 10 (62,5%) из 16 больных с MALT-лимфомой имелся хотя бы один минорный аллель А (AA + GA), в то время как при отсутствии MALT-лимфомы хотя бы один минорный аллель А обнаружен лишь в 32,8 % случаев (ОШ 3,4; 95 % ДИ 1,1–10,7; p = 0,03). Кроме того, была выявлена взаимосвязь генотипа rs7574865 ТТ гена STAT4 с риском развития при СШ тяжелой лейкопении, которая у носителей генотипа ТТ встречалась значимо чаще, чем у лиц с генотипом GG+GT (ОШ 4,9; 95 % ДИ 1,7–14,4; p = 0,004). Полиморфизм гена IRF5 (rs2004640) не был ассоциирован ни с риском развития СШ, ни с его клиническими проявлениями.

   Заключение

   Заключение. Полиморфизмы rs7574865 гена STAT4, rs6920220, rs2230926 гена TNFAIP3 связаны с риском развития либо СШ, либо его тяжелых осложнений – MALT-лимфомы и лейкопении.

   In recent years, more and more data have emerged confirming the contribution of non-HLA genetic markers to the predisposition to thedevelopment of Sjögren's syndrome (SS) and its severe complication, MALT-lymphoma.

   Objective

   Objective: to study the association of polymorphisms of IRF5 (rs2004640), STAT4 (rs7574865), and TNFAIP3 (rs6920220, rs2230926) genes with predisposition to the development of SS and MALT-lymphoma.

   Materials and methods

   Materials and methods. The study included 80 patients with SS and 103 individuals in the control group. Sixteen patients were diagnosed with MALT-lymphoma. Genotyping of polymorphisms of IRF5 (rs2004640), STAT4 (rs7574865), TNFAIP3 (rs6920220, rs2230926) genes was performed by real-time polymerase chain reaction using original allele-specific probes labeled with different fluorescent labels.

   Results and discussion. The distribution of genotypes and alleles of the STAT4 gene differed statistically significantly in the study and control groups of patients (p = 0.0005 and p = 0.0001, respectively). The presence of the homozygous TT genotype increased the risk of developing SS more than eightfold compared to TG+GG genotypes (odds ratio, OR=8.2; 95 % confidence interval, CI 2.5–30.0; p=0.0001)]. The polymorphism of the TNFAIP3 rs2230926 gene was also associated with the risk of developing SS: the presence of the TG genotype significantly increased the probability of developing SS compared to the TT genotype (OR 6.4; 95% CI 1.2–44.3; p = 0.01). The development of MALT-lymphoma was associated with the rs6920220 polymorphism of the TNFAIP3 gene. In 10 out of 16 patients with MALT-lymphoma (62.5 %) at least one minor A allele (AA+GA) was detected, while in patients without MALT-lymphoma only in 32.8 % of patients at least one minor A allele was detected (OR=3.4, CI 1.1–10.7; p=0.03). In addition, a correlation was found between the rs7574865 TT genotype of the STAT4 gene and the risk of developing severe leukopenia in SS, which was significantly more frequent in carriers of the TT genotype than in individuals with the GG + GT genotype (OR 4.9; 95 % CI 1.7–14.4; p = 0.004). Polymorphism of the IRF5 gene (rs2004640) was not associated with risk of developing SS or with clinical manifestations of the disease.

   Conclusion

   Conclusion. Polymorphisms rs7574865 of STAT4 gene, rs6920220, rs2230926 of TNFAIP3 gene are associated either with the risk of developing SS or with severe complications of the disease, MALT-lymphoma and leukopenia.

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