The role of PITX2 rs6817105 and KCNN3 rs13376333 polymorphisms in the risk of atrial fibrillation complicating arterial hypertension.
Received: 2025-12-06 17:29:02
Published: 2025-03-29
Abstract
Aim. To determine the association between polymorphisms of the PITX2 (rs6817105) and KCNN3 (rs13376333) genes and the development of atrial fibrillation (AF) in patients with arterial hypertension (AH) in the Uzbek population.
Materials and methods. The study included 154 patients with AH. Among them, paroxysmal AF was initially diagnosed in 21 patients (13.64%), persistent AF in 44 patients (28.57%), and permanent AF in 89 patients (57.79%). At the beginning of the study, the mean age of patients with AH and AF was 64.1±10.35 years. The control group consisted of AH patients without AF (n=91), with a mean age of 56.03±12.18 years. Clinical and instrumental examinations, including ECG, echocardiography, and Holter monitoring, were performed. Molecular genetic analysis of isolated DNA was carried out using real-time PCR. The association of polymorphisms with AF was assessed using logistic regression analysis and various inheritance models. Statistical analysis was performed using Statistica 10.0 and SNPassoc (R) software.
Results. The study revealed statistically significant associations between the risk of atrial fibrillation development and the PITX2 gene rs6817105 polymorphism as well as the KCNN3 gene rs13376333 polymorphism in Uzbek patients with arterial hypertension. The PITX2 rs6817105 polymorphism showed a strong association with atrial fibrillation: carriage of the minor C allele increased the risk of AF development 2.76-fold under the log-additive inheritance model (OR = 2.76; p = 3.27×10⁻⁷). The KCNN3 rs13376333 polymorphism also demonstrated a significant association with AF. The C allele was significantly more frequent in patients with rhythm disorders and increased the risk of AF development under the log-additive model (OR = 1.63; p = 0.020).
Conclusion. For the first time, an association between the PITX2 gene rs6817105 polymorphism and the KCNN3 gene rs13376333 polymorphism with atrial fibrillation has been identified in AH patients of the Uzbek population. These findings confirm the importance of these genetic markers in the pathogenesis of atrial fibrillation complicated by arterial hypertension and emphasize the relevance of genetic testing in this group of patients.
Keywords
List of references
-
Van Gelder IC, Rienstra M, Bunting KV, Casado-Arroyo R, Caso V va boshq.; ESC ilmiy hujjatlar guruhi. Yevropa Yurak-ko‘krak jarrohligi assotsiatsiyasi (EACTS) bilan hamkorlikda ishlab chiqilgan bo‘lmachalar fibrillyatsiyasini boshqarish bo‘yicha 2024-yilgi ESC ko‘rsatmalari. Eur Heart J. 2024 yil 29 sentyabr;45(36):3314-3414. https://doi.org/10.1093/eurheartj/ehae176. Tuzatish: Eur Heart J. 2025 yil 7 iyul:ehaf306. https://doi.org/10.1093/eurheartj/ehaf306.PMID:39210723.
-
Sasano T, Ihara K, Tanaka T, Furukawa T. Yagona nukleotid polimorfizmi va aylanuvchi biomarkerlardan foydalangan holda bo‘lmachalar fibrillyatsiyasi va insult xavfini baholash. PLoS One. 2023 yil 12 oktyabr;18(10):e0292118. https://doi.org/10.1371/journal.pone.0292118. PMID: 37824462; PMCID: PMC10569505.
-
Kim JA, Chelu MG, Li N. Bo‘lmachalar fibrillyatsiyasi genetikasi. Curr Opin Cardiol. 2021 yil 1 may;36(3):281-287. https://doi.org/10.1097/HCO.0000000000000840. PMID: 33818546; PMCID: PMC8211390.
-
Luo Z., Yan C., Zhang W. va boshq. Xitoy Xan populyatsiyasida KCNN3 genidagi rs13376333 va rs1131820 SNP va bo‘lmachalar fibrillyatsiyasi o‘rtasidagi bog‘liqlik. Klinik kimyo va laboratoriya tibbiyoti. 2014 yil dekabr; 52(12): 1867-1873. https://doi.org/10.1515/cclm-2014-0491.
-
Yao JL, Zhou YF, Yang XJ, Qian XD, Jiang WP. 1q21 xromosomasidagi KCNN3 SNP rs13376333 bo‘lmachalar fibrillyatsiyasi xavfini oshirishi. Xalqaro Yurak Jurnali. 2015;56(5):511-515. https://doi. org/10.1536/ihj.15-133. PMID: 26370375
-
Tomomori S, Nakano Y, Ochi H va boshqalar. 4q25 xromosomadagi rs6817105 varianti sinus tugun disfunksiyasi va chap bo‘lmacha kengayishiga olib keladi. Ilmiy ma’ruzalar.2018 yil 1 oktyabr;8(1):13557.https://doi.org/10.1038/s41598-018-32453-8.PMID: 30275441
-
EACTS bilan hamkorlikda ishlab chiqilgan bo‘lmachalar fibrillyatsiyasini boshqarish bo‘yicha 2016 yilgi ESC ko‘rsatmalari. Eur Heart J (2016) 37 (38): 2893-2962. https://doi.org/https://doi.org/10.1093/ eurheartj/ehw210.
-
Camm AJ, Kirchhof P, Lip GY va boshqalar. Bo‘lmachalar fibrillyatsiyasini boshqarish bo‘yicha ko‘rsatmalar: Yevropa kardiologiya jamiyatining (ESC) bo‘lmachalar fibrillyatsiyasini boshqarish bo‘yicha ishchi guruhi. Europace. 2010; 12: 1360-1420.
-
Sahn D.J., Demaria A., Kisslo J. va boshqalar. M-rejimli exokardiografiyada miqdoriy ko‘rsatkichlar bo‘yicha tavsiyalar: Exokardiografik o‘lchovlar so‘rovi natijalari // Circulation.-1987.-58-jild.- 1072-1082 b.
-
Devereux R.B., Reichek N. Insonda chap qorincha massasini exokardiografik aniqlash// Circulation.-1977.-№55.-613-618 b.
-
Yevropa kardiologiya jamiyati (ESC) va Yevropa gipertenziya jamiyatining (ESH) arterial gipertenziyani boshqarish bo‘yicha ishchi guruhi. Yevropa Yurak Jurnali 2018 - https://doi.org//10.1093/eurheartj/ehy3 39.
-
Zafrir B., Lund L., Laroche C., Ruschitzka F., Crespo-Leiro M., Coats A. va boshqalar; ESC-HFA HF uzoq muddatli registr tadqiqotchilari nomidan. Yurak yetishmovchiligining pasaygan, o‘rta darajali va saqlanib qolgan chiqarish fraksiyasi bilan kechishida bo‘lmachalar fibrillyatsiyasining prognostik ahamiyati: Yevropa Kardiologiya Jamiyatining Yurak Yetishmovchiligi uzoq muddatli registridan 14 964 bemor haqida hisobot. European Heart Journal (2018) 39, 4277-4284.
-
Stanley Nattel MD Masahide Harada MD, PhD. Bo‘lmachalar qayta modellanishi va bo‘lmachalar fibrillyatsiyasi: So‘nggi yutuqlar va translatsion istiqbollar Journal of the American College of Cardiology (2014) 22, 2365-2345 https://doi.org/10.1016/j.jacc.2014.02.555.
-
Ott A., Breteler M.M., de Bruyne M.C. va boshqalar. Aholiga asoslangan tadqiqotda bo‘lmachalar fibrillyatsiyasi va demensiya. Rotterdam tadqiqoti. Insult. 1997;28:316-321.
-
Marwick TH, Gillebert TC, Aurigemma G, Chirinos J, Derumeaux G, Galderisi M va boshqalar. Katta yoshli gipertoniya bemorlarida exokardiografiyadan foydalanish bo‘yicha tavsiyalar: Yevropa Kardiovaskulyar Tasvirlash Assotsiatsiyasi (EACVI) va Amerika Exokardiografiya Jamiyati (ASE) hisoboti. Eur Heart J Cardiovasc Imaging 2015;16:577-605.
-
de Simone G, Kitzman DW, Chinali M, Oberman A, Hopkins PN, Rao DC va boshqalar. Chap qorinchaning konsentrik geometriyasi gipertoniya kasalligida bo‘shashishning buzilishi bilan bog‘liq: HyperGEN tadqiqoti. Eur Heart J 2005;26:1039-1045.
-
Domanski M, Mitchell G, Pfeffer M, Neaton JD, Norman J, Svendsen K va boshqalar, MRFIT tadqiqot guruhi. Puls bosimi va yurak-qon tomir kasalliklari bilan bog‘liq o‘lim: Ko‘p xavf omillarini nazorat qilish bo‘yicha interventsion sinov (MRFIT) ning kuzatuv tadqiqoti. JAMA 2002;287:2677-2683.
-
Yaghi S, Moon YP, Mora-McLaughlin C, Willey JZ, Cheung K, Di Tullio MR va boshqalar. Chap bo‘lmacha kengayishi va insultning takrorlanishi: Shimoliy Manhattan insult tadqiqoti. Stroke 2015;46:1488-1493.
-
Losi MA, Izzo R, De Marco M, Canciello G, Rapacciuolo A, Trimarco V va boshqalar. Yurak-qon tomir tizimining ultratovush tekshiruvi arterial gipertenziyada bo‘lmachalar fibrillyatsiyasini bashorat qilishga yordam beradi: Campania Salute tarmog‘i. Int J Cardiol 2015;199:290-295.
-
Douglas PS. Chap bo‘lmacha: surunkali diastolik disfunksiya va yurak-qon tomir kasalliklari xavfining biomarkeri. J Am Coll Cardiol 2003;42:1206-1207.
-
Kuznetsova T, Haddad F, Tikhonoff V, Kloch-Badelek M, Ryabikov A, Knez J va boshqalar, Gipertenziyada genlar bo‘yicha Yevropa loyihasi tadqiqotchilari. Aholiga asoslangan tadqiqotlarda chap qorincha va bo‘lmacha tuzilishini miqyoslashning ta’siri va muammolari. J Hypertens 2016;34:1186-1194.
-
Sinner MF, Ellinor PT, Meitinger T, Benjamin EJ, Kääb S. Bo‘lmachalar fibrillyatsiyasining butun genom assotsiatsiyasi tadqiqotlari: o‘tmish, hozirgi va kelajak. Kardiovask Res. 2011; 89: 701-709.
-
Abdullaeva G.J., Abdullaev A.A., Kevorkov A.G., Abduvalieva G.A., Zakirov N.U., Kurbanov R.D. O‘ZBEK BEMORLARIDA ATFB5 GENINING rs2200733 POLIMORFIZMI VA BO‘LMACHALAR FIBRILLYATSIYASI O‘RTASIDAGI O‘ZARO BOG‘LIQLIK. Turk Kardiyol Dern Ars 2021;49(5):404-409 https://doi.org/10.5543/tkda.2021.08434.
-
G. M. Rajabova, G. J. Abdullaeva, D. V. Zakirova, M. T. Po‘latova, N. X. Sherbadalova, M. N. Xatamova va boshqalar. Arterial gipertenziyali o‘zbek bemorlarda 4q25/PITX2 SNP rs6817105 va bo‘lmachalar fibrillyatsiyasi. International Journal of Biomedicine. 2023;13(3):72-78. https://doi.org/0.21103/Article1 3(3)_OA3.
-
Ferran A., Alegret J.M., Subirana I. va boshqalar. Ispaniya aholisida rs2200733 va rs7193343 genetik variantlari hamda bo‘lmachalar fibrillyatsiyasi o‘rtasidagi bog‘liqlik va oldingi tadqiqotlarning meta-tahlili. Rev. Esp. Kardiol. 2014;67(10):822-829.
-
Kalinderi K, Fragakis N. va boshqalar. Yunon aholisida 4q25 xromosomasidagi rs2200733 polimorfizmi va bo‘lmachalar fibrillyatsiyasi o‘rtasidagi bog‘liqlik. Hellenic J Cardiol 2015; 56: 224-229.
-
Rattanawong P., Chenbhanich J. va boshqalar. 4q25 xromosoma varianti kateter ablatsiyasidan keyin bo‘lmachalar fibrillyatsiyasining qaytarilishi bilan bog‘liq: tizimli sharh va meta-tahlil. J Atr Fibrillation. 2018-yil aprel; 10(6): 1666.
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Copyright (c) 2026 Z.T. Mashkurova, G.J. Abdullaeva, D.V. Zakirova, G.M. Radjabova, G.A. Khamidullaeva, A.A. Abdullaev, B.I. Rozibaev (Author)
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