Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis

Yıl 2017, Cilt: 16 Sayı: 3, 106 - 109, 20.11.2017

Fatma Ebru Akın Gülay Güleç Ceylan Aylin Demirezer Bolat Öykü Tayfur Yürekli Mustafa Tahtacı Eyüp Selvi Naciye Şemnur Büyükaşık Osman Ersoy

https://doi.org/10.17941/agd.351668

Öz

Background and Aims: Primary biliary cirrhosis is a chronic cholestatic autoimmune liver disease. Genetic factors appear to be involved in the pathogenesis of primary biliary cirrhosis. 1,25 dihydroxyvitamin D3, is a secosteroid hormone that mediates its effects through the vitamin D receptor. A few polymorphisms have been defined in the vitamin D receptor gene so far. Autoimmune diseases have been found to be associated with vitamin D receptor gene polymorphisms. We evaluated the relationship between vitamin D receptor gene polymorphisms and primary biliary cirrhosis. Materials and Methods: Primary biliary cirrhosis patients who were treated in the Atatürk Research and Teaching Hospital Gastroenterology Department, from 2007-2012 are included. The study group included 16 primary biliary cirrhosis patients and 28 healthy people. Biliary obstruction was excluded using imaging modalities. Of the 16 patients, 13 had liver biopsies consistent with primary biliary cirrhosis. There were no concomitant liver diseases. Vitamin D receptor genotyping was done by the polymerase chain reaction–restriction fragment length polymorphism with BsmI, ApaI, and TaqI endonucleases. Results: Of the 16 patients, 14 were female. The average age was 58.4±6.6 years. Control group patients were age- and gender-matched. No differences in vitamin D receptor gene BsmI, ApaI, and TaqI polymorphisms were found between the primary biliary cirrhosis and control groups. Conclusion: We did not find any relationship between vitamin D receptor gene BsmI, ApaI, and TaqI polymorphisms and primary biliary cirrhosis.

Anahtar Kelimeler

Polymorphisms, primary biliary cirrhosis, vitamin D receptor

Vitamin D reseptör gen polimorfizmi ile primer biliyer siroz ilişkisi

Öz

Giriş ve Amaç: Primer biliyer siroz, kronik kolestatik otoimmün karaciğer hastalığıdır. Primer biliyer sirozun patogenezinde genetik faktörler rol oynamaktadır. 1,25-dihidroksivitamin D3 (1,25(OH)2D3), sekosteroid hormondur. 1,25(OH)2D3 etkilerini vitamin D reseptör aracılığı ile gösterir. Vitamin D reseptör geninde birkaç polimorfizm bildirilmişdir. Bazı otoimmün hastalıklar vitamin D reseptör gen polimorfizmi ile ilişkili bulunmuştur. Biz bu çalışmada primer biliyer siroz ile vitamin D reseptör gen polimorfizminin ilişkisini değerlendirdik. Gereç ve Yöntem: Atatürk Eğitim ve Araştırma Hastanesi Gastoenteroloji Kliniği’nde, 2007-2012 yılları arasında primer biliyer siroz tanısı ile takip edilmekte olan hastalar alındı. Çalışmaya 16 primer biliyer siroz ve 28 sağlıklı gönüllü dahil edildi. Biliyer obstrüksiyon varlığı görüntüleme yöntemleri ile ekarte edildi. 16 hastanın 13’ünde karaciğer biyopsisi vardı ve primer biliyer siroz ile uyumlu idi. Eşlik eden başka karaciğer hastalığı yoktu. Vitamin D reseptör genotiplendirilmesi; BsmI, ApaI, TaqI endonükleazları kullanılarak polimerize zincir reaksiyonu-restriksiyon parçacık uzunluk polmorfizmi ile yapıldı. Bulgular: Hastaların 14’ü kadın, 2’si erkekdi. Hastaların yaş ortalaması 58,4±6,6 idi. Kontrol grubu yaş ve cinsiyet olarak denkti. Vitamin D reseptör gen BsmI, ApaI, TaqI polimorfizmlerinin primer biliyer siroz ve konrol grubunda farklı olmadığı görüldü. Sonuç: Biz bu çalışmada, primer biliyer siroz ile vitamin D reseptör gen BsmI, ApaI, TaqI polimorfizmleri arasında ilişki saptamadık.

Anahtar Kelimeler

Polimorfizm, primer biliyer siroz, vitamin D reseptör

Kaynakça

• 1. Kaplan MM, Gershwin ME. Primary biliary cirrhosis. N Engl J Med 2005;353:1261-73. 2. Gershwin ME, Mackay IR. The causes of primary biliary cirrhosis: Convenient and inconvenient truths. Hepatology 2008;47:737-45. 3. Lazaridis KN, Juran BD, Boe GM, et al. Increased prevalence of antimitochondrial antibodies in first-degree relatives of patients with primary biliary cirrhosis. Hepatology 2007;46:785-92. 4. Chen RR, Han ZY, Li JG, et al. Cytotoxic T-lymphocyte antigen 4 gene +49A/G polymorphism significantly associated with susceptibility to primary biliary cirrhosis: a meta-analysis. J Dig Dis 2011;12:428-35. 5. Peelen E, Knippenberg S, Muris AH, et al. Effects of vitamin D on the peripheral adaptive immune system: a review. Autoimmun Rev 2011;10:733-43. 6. Souberbielle JC, Body JJ, Lappe JM, et al. Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice. Autoimmun Rev 2010;9:709-15. 7. Norman AW. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr 2008;88:491S-499S. 8. Morrison NA, Qi JC, Tokita A, et al. Prediction of bone density from vitamin D receptor alleles. Nature 1994;367:284-7. 9 Halmos B, Szalay F, Cserniczky T, et al. Association of primary biliary cirrhosis with vitamin D receptor BsmI genotype polymorphism in a Hungarian population. Dig Dis Sci 2000;45:1091-5. 10. Vogel A, Strassburg CP, Manns MP. Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis and autoimmune hepatitis. Hepatology 2002;35:126-31. 11. Lakatos LP, Bajnok E, Hegedus D. Vitamin D receptor, oestrogen receptor-alpha gene and interleukin-1 receptor antagonist gene polymorphisms in Hungarian patients with primary biliary cirrhosis. Eur J Gastroenterol Hepatol 2002;14:733-40. 12. Fan L, Tu X, Zhu Y, et al. Genetic association of vitamin D receptor polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese. J Gastroenterol Hepatol 2005;20:249-55. 13. Tanaka A, Nezu S, Uegaki S, et al. Vitamin D receptor polymorphisms are associated with increased susceptibility to primary biliary cirrhosis in Japanese and Italian populations. J Hepatol 2009;50:1202-9. 14. Kempińska-Podhorecka A, Wunsch E, Jarowicz T, et al. Vitamin D receptor polymorphisms predispose to primary biliary cirrhosis and severity of the disease in polish population. Gastroenterol Res Pract 2012;2012:408723. 15. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol 2009;51:237-67. 16. Li YJ, Tang YW, Shi YQ, et al. Polymorphisms in the vitamin D receptor gene and risk of primary biliary cirrhosis: A meta-analysis. J Gastroenterol Hepatol 2014;29:706-15. 17. Mo C, Lu Y, Deng Y, et al. Lack of association between vitamin D receptor gene ApaI, BsmI, and TaqI polymorphisms and primary biliary cirrhosis risk: A meta-analysis. Tumour Biol 2014;35:4913-20. 18. Fang F, Wang J, Pan J, et al. Relationship between vitamin D (1,25-dihydroxyvitamin D3) receptor gene polymorphisms and primary biliary cirrhosis risk: A meta-analysis. Genet Mol Res 2015;14:981-8.