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Ankilozan spondilitli hastalarda BMP-6 rs267196 ve rs267192 genetik polimorfizmi

Year 2019, Volume: 76 Issue: 2, 183 - 194, 01.06.2019

Abstract

Amaç: Kemik morfogenetik proteinlerinin BMP’ler çeşitli popülasyonlarda ankilozan spondilit AS ile ilişkili olduğu bildirilmiştir. Bu çalışmanın amacı, BMP-6 gen polimorfizminin rs267192 ve rs267196 AS ile ilişkisini belirlemek ve aralarındaki ilişkileri klinik ve laboratuvar verilerine dayanarak değerlendirmektir.Yöntem: Bu çalışma, Ağustos 2013 - Kasım 2013 tarihleri arasında Çanakkale Onsekiz Mart Üniversitesi Sağlık Uygulama ve Araştırma Hastanesi Fizik Tedavi ve Rehabilitasyon Polikliniğinde gerçekleştirilmiştir. 42 AS hastası ve 58 sağlıklı kontrol BMP-6 rs267192 ve rs267196 polimorfizmi için ters transkripsiyonpolimeraz zincir reaksiyonu RT-PCR analizi ile kontrol edilmiştir. Klinik veriler olarak yaş, cinsiyet, vücut kitle indeksi, C-reaktif protein CRP , eritrosit sedimantasyon hızı, bath ankilozan spondilit hastalık aktivite indeksi BASDAI ve HLA-27 pozitifliği araştırılmıştır. BMP-6 polimorfizmi ile laboratuvar bulguları arasındaki ilişki değerlendirilmiştir. Bulgular: BMP-6 rs267196 için sırasıyla AA, AT ve TT genotiplerinin sıklığı AS hastalarında %9,5 n= 4 , %38,1 n= 16 ve %52,4 n= 22 ve kontrol grubunda %15,5 n = 9 , %44,8 n= 26 ve %39,7 n = 23 bulunmuştur. BMP-6 rs267196 A allel taşıyıcılar T alelline karşı 1,4 kat daha yüksek risk ve rs267192 T allel taşıyıcıları C alelline karşı AS için 1,08 kat daha yüksek risk taşıdığı görülmüştür. AS ile kontrol grupları arasında yaş, cinsiyet ve BMI değerleri açısından anlamlı bir fark bulunmamıştır. AS grubunun CRP ve sedimantasyon düzeyi kontrol grubundan anlamlı olarak yüksek olduğu görülmüştür p

References

  • 1. Cortes A, Hadler J, Pointon JP, Robinson PC, Karaderi T, Leo P, et al. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nature genetics, 2013;45(7):730.
  • 2. Coşan F, Gül A. Ankilozan spondilit patogenezi. Turkiye Klinikleri J Int Med Sci, 2007;3(25):13-9.
  • 3. Brown MA, Kenna T, Wordsworth BP. Genetics of ankylosing spondylitis-insights into pathogenesis. Nat Rev Rheumatol, 2016;12(2):81-91.
  • 4. Joo YB, Bang SY, Kim TH, Shim SC, Lee S, Joo KB, et al. Bone morphogenetic protein 6 polymorphisms are associated with radiographic progression in ankylosing spondylitis. PloS One, 2014;9(8):e104966.
  • 5. Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Gen, 2007;39(11):1329.
  • 6. Grgurevic L, Christensen GL, Schulz TJ, Vukicevic S. Bone morphogenetic proteins in inflammation, glucose homeostasis and adipose tissue energy metabolism. Cytokine & Growth Factor Rev, 2016;27:105-18.
  • 7. Liao H, Lin Y, Tsai C, Chou T. Bone morphogenetic proteins and dickkopf-1 in ankylosing spondylitis. Scand J Rheumatol, 2018;47(1):56-61.
  • 8. Baldwin C, Nolan VG, Wyszynski DF, Ma Q-L, Sebastiani P, Embury SH, et al. Association of klotho, bone morphogenic protein 6, and annexin A2 polymorphisms with sickle cell osteonecrosis. Blood, 2005;106(1):372-5.
  • 9. Mahmoud A, Fayez D, Gabal MMA, Hamza SMH, Badr T. Insight on bone morphogenetic protein 7 in ankylosing spondylitis and its association with disease activity and radiographic damage. Electronic Physician, 2016;8(7):2670.
  • 10. Chen HA, Chen CH, Lin YJ, Chen PC, Chen WS, Lu CL, et al. Association of bone morphogenetic proteins with spinal fusion in ankylosing spondylitis. J Rheumatol, 2010;37(10):2126-32.
  • 11. Jane Jr JA, Dunford BA, Kron A, Pittman DD, Sasaki T, Li JZ, et al. Ectopic osteogenesis using adenoviral bone morphogenetic protein (BMP)-4 and BMP-6 gene transfer. MolTher, 2002;6(4):464-70.
  • 12. Wendling D, Cedoz JP, Racadot E, Dumoulin G. Serum IL-17, BMP-7, and bone turnover markers in patients with ankylosing spondylitis. Joint Bone Spine, 2007;74(3):304-5.
  • 13. Akbulut E, Erdemir A, Özgen M, Baskin Y, Güleç F, Turgut Balik D. Genotyping and analysis of rs27037 polymorphism for ankylosing spondylitis. Sigma J Eng Nat Sci, 2015;6(1):117-25
  • 14. van der Linden S, Brown M, Kenna T, Maksymowych W, Robinson P. Ankylosing spondylitis. In: Firestein G, Budd R, Gabriel SE, McInnes IB, O’Dell J, eds. Kelley and Firestein’s Textbook of Rheumatology. 10th ed. Amsterdam: Elsevier, 2017.
  • 15. Dakwar E, Reddy J, Vale FL, Uribe JS. A review of the pathogenesis of ankylosing spondylitis. Neurosurg Focus, 2008;24(1):E2. doi: 10.3171/ FOC/2008/24/1/E2.
  • 16. Kim TH, Uhm WS, Inman RD. Pathogenesis of ankylosing spondylitis and reactive arthritis. Curr Opin Rheumatol, 2005;17(4):400-5.
  • 17. Na KS, Kim TH, Rahman P, Peddle L, Choi CB, Inman RD. Analysis of single nucleotide polymorphisms in toll-like receptor 4 shows no association with ankylosing spondylitis in a Korean population. Rheumatol Int, 2008;28(7):627-30.
  • 18. Chaouch L, Kalai M, Jbara MB, Chaabene AB, Darragi I, Chaouachi D, et al. Association between rs267196 and rs267201 of BMP6 gene and osteonecrosis among sickle cell aneamia patients. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2015;159(1):145-9.
  • 19. Brown MA, Kenna T, Wordsworth BP. Genetics of ankylosing spondylitis—insights into pathogenesis. Nat Rev Rheumatol, 2016;12(2):81.
  • 20. Aşkın A. Ankilozan spondilit hastalarında nötrofil/ lenfosit oranı, trombosit/lenfosit oranı ve ortalama trombosit hacminin değerlendirilmesi. Cukurova Med J, 41(3):479-84.
  • 21. Lories RJ, Luyten FP. Bone morphogenetic protein signaling in joint homeostasis and disease. Cytokine & Growth Factor Rev, 2005;16(3):287-98.
  • 22. Ashley Koch AE, Elliott L, Kail ME, De Castro LM, Jonassaint J, Jackson TL, et al. Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease. Blood, 2008;111(12):5721-6.
  • 23. Yan L, Chang Z, Liu Y, Li Y, He B, Hao D. A single nucleotide polymorphism in the human bone morphogenetic protein-2 gene (109T> G) affects the smad signaling pathway and the predisposition to ossification of the posterior longitudinal ligament of the spine. Chin Med J, 2013;126(6):1112-8.
  • 24. McHugh K, Bowness P. The link between HLA-B27 and SpA—new ideas on an old problem. Rheumatol, 2012;51(9):1529-39.
  • 25. Akbal A, Reşorlu H, Gökmen F, Savaş Y, Zateri Ç, Sargin B, et al. The relationship between C‐reactive protein rs3091244 polymorphism and ankylosing spondylitis. Int J Dis, 2016;19(1):43-8.
  • 26. Tam LS, Gu J, Yu D. Pathogenesis of ankylosing spondylitis. Nat Rev Rheumatol, 2010;6(7):399.
  • 27. Wolf J, Fasching P. Ankylosing spondylitis. Wien Med Wochenschr, 2010;160(9-10):211-4.
  • 28. Çay HF, Kaçar C. Ankilozan spondilit epidemiyolojisi. Turkiye Klinikleri J Immunol- Rheumatol Special Topics, 2011;4(1):1-6.
  • 29. Khan MA. Remarkable polymorphism of HLA-B27: an ongoing saga. Curr Rheumatol Rep, 2010;12(5):337- 41.
  • 30. Cauli A, Dessole G, Fiorillo M, Vacca A, Mameli A, Bitti P, et al. Increased level of HLA‐B27 expression in ankylosing spondylitis patients compared with healthy HLA‐B27‐positive subjects: a possible further susceptibility factor for the development of disease. Rheumatol, 2002;41(12):1375-9.
  • 31. Wang CM, Ho HH, Chang SW, Wu YJ, Lin JC, Chang PY, et al. ERAP1 genetic variations associated with HLA-B27 interaction and disease severity of syndesmophytes formation in Taiwanese ankylosing spondylitis. Arthritis Research Ther, 2012;14(3):R125.
  • 32. Ulug P, Vasavda N, Awogbade M, Cunningham J, Menzel S, Thein SL. Association of sickle avascular necrosis with bone morphogenic protein 6. Ann Hematol, 2009;88(8):803-5.
  • 33. Pekacar FS, Akdoğan A, Hayran M, Çolak R, Yılmaz E. Ankilozan spondilit ile HLA-B27, MEFV gen mutasyonları, ERAP1, IL12B ve IL23R gen polimorfizmleri arasındaki ilişki. Turk Biyokimya Derg, 2014;39(4),482-7.
  • 34. Temel Ş. Primer sjögren sendromu, ankilozon spondilit ve ankilozan spondilitle birlikte sjögren sendromu tanılı hastalarda IL 23 reseptör gen polimorfizminin karşılaştırılması. Tıpta Uzmanlık Tezi, Pamukkale Üni Tıp Fak İç Hast ABD, 2014.
  • 35. Akbulut E, Erdemir A, Özgen M, Baskin Y. Genotyping and analysis of rs27037 polymorphism for ankylosing spondylit. Sigma J Eng & Nat Sci, 2015; 6(1): 117-125.
  • 36. Chen R, Yao L, Meng T, Xu W. The association between seven ERAP1 polymorphisms and ankylosing spondylitis susceptibility: a metaanalysis involving 8,530 cases and 12,449 controls. Rheumatol Int, 2012;32(4):909-14.
  • 37. Zhang Z, Dai D, Yu K, Yuan F, Jin J, Ding L, et al. Association of HLA‐B27 and ERAP1 with ankylosing spondylitis susceptibility in Beijing Han Chinese. HLA, 2014;83(5):324-9.
  • 38. Evans DM, Spencer CC, Pointon JJ, Su Z, Harvey D, Kochan G, et al. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat Gen, 2011;43(8):761.

Genetic polymorphism of BMP-6 gene rs267196 and rs267192 in patients with Ankylosing spondylitis

Year 2019, Volume: 76 Issue: 2, 183 - 194, 01.06.2019

Abstract

Objective: Bone morphogenetic proteins BMPs have been documented to be associated with ankylosing spondylitis AS in several populations. The goal of the present study was to determine the association of the BMP-6 gene polymorphism rs267192 and rs267196 with AS and to evaluate the relationships between them based on clinical and laboratory data.Methods: This study was conducted during August and November 2013 at the physical therapy and rehabilitation outpatient clinics of Çanakkale Onsekiz Mart University Research and Practice Hospital. 42 AS patients and 58 healthy controls were checked with reverse transcription-polymerase chain reaction RT-PCR analysis for BMP-6 rs267192 and rs267196 polymorphism. Clinical data as age, gender, body mass index, C-reactive protein CRP , erythrocyte sedimentation rate, bath ankylosing spondylitis disease activity index BASDAI , and HLA-27 positivity were assessed. It was evaluated the relationship between the BMP-6 polymorphism and laboratory findings.Results: The frequencies of AA, AT, and TT genotypes for BMP-6 rs267196 were 9.5% n=4 , 38.1% n=16 , and 52.4% n=22 in AS patients, and 15.5% n=9 , 44.8% n=26 , and 39.7% n=23 in controls respectively. BMP-6 rs267196 A allele carriers versus T ancient allele had 1.4-fold higher risk and rs267192 T allele carriers versus C ancient allele had 1.08-fold higher risk for AS. There was no significant difference between AS and control groups in terms of age, gender and BMI. The CRP and sedimentation levels of the AS group were significantly higher than the control group p

References

  • 1. Cortes A, Hadler J, Pointon JP, Robinson PC, Karaderi T, Leo P, et al. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nature genetics, 2013;45(7):730.
  • 2. Coşan F, Gül A. Ankilozan spondilit patogenezi. Turkiye Klinikleri J Int Med Sci, 2007;3(25):13-9.
  • 3. Brown MA, Kenna T, Wordsworth BP. Genetics of ankylosing spondylitis-insights into pathogenesis. Nat Rev Rheumatol, 2016;12(2):81-91.
  • 4. Joo YB, Bang SY, Kim TH, Shim SC, Lee S, Joo KB, et al. Bone morphogenetic protein 6 polymorphisms are associated with radiographic progression in ankylosing spondylitis. PloS One, 2014;9(8):e104966.
  • 5. Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Gen, 2007;39(11):1329.
  • 6. Grgurevic L, Christensen GL, Schulz TJ, Vukicevic S. Bone morphogenetic proteins in inflammation, glucose homeostasis and adipose tissue energy metabolism. Cytokine & Growth Factor Rev, 2016;27:105-18.
  • 7. Liao H, Lin Y, Tsai C, Chou T. Bone morphogenetic proteins and dickkopf-1 in ankylosing spondylitis. Scand J Rheumatol, 2018;47(1):56-61.
  • 8. Baldwin C, Nolan VG, Wyszynski DF, Ma Q-L, Sebastiani P, Embury SH, et al. Association of klotho, bone morphogenic protein 6, and annexin A2 polymorphisms with sickle cell osteonecrosis. Blood, 2005;106(1):372-5.
  • 9. Mahmoud A, Fayez D, Gabal MMA, Hamza SMH, Badr T. Insight on bone morphogenetic protein 7 in ankylosing spondylitis and its association with disease activity and radiographic damage. Electronic Physician, 2016;8(7):2670.
  • 10. Chen HA, Chen CH, Lin YJ, Chen PC, Chen WS, Lu CL, et al. Association of bone morphogenetic proteins with spinal fusion in ankylosing spondylitis. J Rheumatol, 2010;37(10):2126-32.
  • 11. Jane Jr JA, Dunford BA, Kron A, Pittman DD, Sasaki T, Li JZ, et al. Ectopic osteogenesis using adenoviral bone morphogenetic protein (BMP)-4 and BMP-6 gene transfer. MolTher, 2002;6(4):464-70.
  • 12. Wendling D, Cedoz JP, Racadot E, Dumoulin G. Serum IL-17, BMP-7, and bone turnover markers in patients with ankylosing spondylitis. Joint Bone Spine, 2007;74(3):304-5.
  • 13. Akbulut E, Erdemir A, Özgen M, Baskin Y, Güleç F, Turgut Balik D. Genotyping and analysis of rs27037 polymorphism for ankylosing spondylitis. Sigma J Eng Nat Sci, 2015;6(1):117-25
  • 14. van der Linden S, Brown M, Kenna T, Maksymowych W, Robinson P. Ankylosing spondylitis. In: Firestein G, Budd R, Gabriel SE, McInnes IB, O’Dell J, eds. Kelley and Firestein’s Textbook of Rheumatology. 10th ed. Amsterdam: Elsevier, 2017.
  • 15. Dakwar E, Reddy J, Vale FL, Uribe JS. A review of the pathogenesis of ankylosing spondylitis. Neurosurg Focus, 2008;24(1):E2. doi: 10.3171/ FOC/2008/24/1/E2.
  • 16. Kim TH, Uhm WS, Inman RD. Pathogenesis of ankylosing spondylitis and reactive arthritis. Curr Opin Rheumatol, 2005;17(4):400-5.
  • 17. Na KS, Kim TH, Rahman P, Peddle L, Choi CB, Inman RD. Analysis of single nucleotide polymorphisms in toll-like receptor 4 shows no association with ankylosing spondylitis in a Korean population. Rheumatol Int, 2008;28(7):627-30.
  • 18. Chaouch L, Kalai M, Jbara MB, Chaabene AB, Darragi I, Chaouachi D, et al. Association between rs267196 and rs267201 of BMP6 gene and osteonecrosis among sickle cell aneamia patients. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2015;159(1):145-9.
  • 19. Brown MA, Kenna T, Wordsworth BP. Genetics of ankylosing spondylitis—insights into pathogenesis. Nat Rev Rheumatol, 2016;12(2):81.
  • 20. Aşkın A. Ankilozan spondilit hastalarında nötrofil/ lenfosit oranı, trombosit/lenfosit oranı ve ortalama trombosit hacminin değerlendirilmesi. Cukurova Med J, 41(3):479-84.
  • 21. Lories RJ, Luyten FP. Bone morphogenetic protein signaling in joint homeostasis and disease. Cytokine & Growth Factor Rev, 2005;16(3):287-98.
  • 22. Ashley Koch AE, Elliott L, Kail ME, De Castro LM, Jonassaint J, Jackson TL, et al. Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease. Blood, 2008;111(12):5721-6.
  • 23. Yan L, Chang Z, Liu Y, Li Y, He B, Hao D. A single nucleotide polymorphism in the human bone morphogenetic protein-2 gene (109T> G) affects the smad signaling pathway and the predisposition to ossification of the posterior longitudinal ligament of the spine. Chin Med J, 2013;126(6):1112-8.
  • 24. McHugh K, Bowness P. The link between HLA-B27 and SpA—new ideas on an old problem. Rheumatol, 2012;51(9):1529-39.
  • 25. Akbal A, Reşorlu H, Gökmen F, Savaş Y, Zateri Ç, Sargin B, et al. The relationship between C‐reactive protein rs3091244 polymorphism and ankylosing spondylitis. Int J Dis, 2016;19(1):43-8.
  • 26. Tam LS, Gu J, Yu D. Pathogenesis of ankylosing spondylitis. Nat Rev Rheumatol, 2010;6(7):399.
  • 27. Wolf J, Fasching P. Ankylosing spondylitis. Wien Med Wochenschr, 2010;160(9-10):211-4.
  • 28. Çay HF, Kaçar C. Ankilozan spondilit epidemiyolojisi. Turkiye Klinikleri J Immunol- Rheumatol Special Topics, 2011;4(1):1-6.
  • 29. Khan MA. Remarkable polymorphism of HLA-B27: an ongoing saga. Curr Rheumatol Rep, 2010;12(5):337- 41.
  • 30. Cauli A, Dessole G, Fiorillo M, Vacca A, Mameli A, Bitti P, et al. Increased level of HLA‐B27 expression in ankylosing spondylitis patients compared with healthy HLA‐B27‐positive subjects: a possible further susceptibility factor for the development of disease. Rheumatol, 2002;41(12):1375-9.
  • 31. Wang CM, Ho HH, Chang SW, Wu YJ, Lin JC, Chang PY, et al. ERAP1 genetic variations associated with HLA-B27 interaction and disease severity of syndesmophytes formation in Taiwanese ankylosing spondylitis. Arthritis Research Ther, 2012;14(3):R125.
  • 32. Ulug P, Vasavda N, Awogbade M, Cunningham J, Menzel S, Thein SL. Association of sickle avascular necrosis with bone morphogenic protein 6. Ann Hematol, 2009;88(8):803-5.
  • 33. Pekacar FS, Akdoğan A, Hayran M, Çolak R, Yılmaz E. Ankilozan spondilit ile HLA-B27, MEFV gen mutasyonları, ERAP1, IL12B ve IL23R gen polimorfizmleri arasındaki ilişki. Turk Biyokimya Derg, 2014;39(4),482-7.
  • 34. Temel Ş. Primer sjögren sendromu, ankilozon spondilit ve ankilozan spondilitle birlikte sjögren sendromu tanılı hastalarda IL 23 reseptör gen polimorfizminin karşılaştırılması. Tıpta Uzmanlık Tezi, Pamukkale Üni Tıp Fak İç Hast ABD, 2014.
  • 35. Akbulut E, Erdemir A, Özgen M, Baskin Y. Genotyping and analysis of rs27037 polymorphism for ankylosing spondylit. Sigma J Eng & Nat Sci, 2015; 6(1): 117-125.
  • 36. Chen R, Yao L, Meng T, Xu W. The association between seven ERAP1 polymorphisms and ankylosing spondylitis susceptibility: a metaanalysis involving 8,530 cases and 12,449 controls. Rheumatol Int, 2012;32(4):909-14.
  • 37. Zhang Z, Dai D, Yu K, Yuan F, Jin J, Ding L, et al. Association of HLA‐B27 and ERAP1 with ankylosing spondylitis susceptibility in Beijing Han Chinese. HLA, 2014;83(5):324-9.
  • 38. Evans DM, Spencer CC, Pointon JJ, Su Z, Harvey D, Kochan G, et al. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat Gen, 2011;43(8):761.
There are 38 citations in total.

Details

Primary Language English
Journal Section Research Article
Authors

Özlem Öztopuz This is me

Fatma Sılan This is me

Özlem Coşkun This is me

Ayla Akbal This is me

Publication Date June 1, 2019
Published in Issue Year 2019 Volume: 76 Issue: 2

Cite

APA Öztopuz, Ö., Sılan, F., Coşkun, Ö., Akbal, A. (2019). Genetic polymorphism of BMP-6 gene rs267196 and rs267192 in patients with Ankylosing spondylitis. Türk Hijyen Ve Deneysel Biyoloji Dergisi, 76(2), 183-194.
AMA Öztopuz Ö, Sılan F, Coşkun Ö, Akbal A. Genetic polymorphism of BMP-6 gene rs267196 and rs267192 in patients with Ankylosing spondylitis. Turk Hij Den Biyol Derg. June 2019;76(2):183-194.
Chicago Öztopuz, Özlem, Fatma Sılan, Özlem Coşkun, and Ayla Akbal. “Genetic Polymorphism of BMP-6 Gene rs267196 and rs267192 in Patients With Ankylosing Spondylitis”. Türk Hijyen Ve Deneysel Biyoloji Dergisi 76, no. 2 (June 2019): 183-94.
EndNote Öztopuz Ö, Sılan F, Coşkun Ö, Akbal A (June 1, 2019) Genetic polymorphism of BMP-6 gene rs267196 and rs267192 in patients with Ankylosing spondylitis. Türk Hijyen ve Deneysel Biyoloji Dergisi 76 2 183–194.
IEEE Ö. Öztopuz, F. Sılan, Ö. Coşkun, and A. Akbal, “Genetic polymorphism of BMP-6 gene rs267196 and rs267192 in patients with Ankylosing spondylitis”, Turk Hij Den Biyol Derg, vol. 76, no. 2, pp. 183–194, 2019.
ISNAD Öztopuz, Özlem et al. “Genetic Polymorphism of BMP-6 Gene rs267196 and rs267192 in Patients With Ankylosing Spondylitis”. Türk Hijyen ve Deneysel Biyoloji Dergisi 76/2 (June 2019), 183-194.
JAMA Öztopuz Ö, Sılan F, Coşkun Ö, Akbal A. Genetic polymorphism of BMP-6 gene rs267196 and rs267192 in patients with Ankylosing spondylitis. Turk Hij Den Biyol Derg. 2019;76:183–194.
MLA Öztopuz, Özlem et al. “Genetic Polymorphism of BMP-6 Gene rs267196 and rs267192 in Patients With Ankylosing Spondylitis”. Türk Hijyen Ve Deneysel Biyoloji Dergisi, vol. 76, no. 2, 2019, pp. 183-94.
Vancouver Öztopuz Ö, Sılan F, Coşkun Ö, Akbal A. Genetic polymorphism of BMP-6 gene rs267196 and rs267192 in patients with Ankylosing spondylitis. Turk Hij Den Biyol Derg. 2019;76(2):183-94.