Araştırma Makalesi
BibTex RIS Kaynak Göster

Türkiye’deki postmenopozal kadınlarda osteoprotegerin A163G ve T245G gen polimorfizmleri ile kemik mineral yoğunluğu arasındaki ilişkinin analizi

Yıl 2018, Cilt: 2 Sayı: 3, 222 - 229, 30.12.2018

Öz

Amaç: Osteoprotegerin
(OPG), osteoporoza yatkınlık ile ilgili en önemli aday genlerden biridir. Bu
çalışmanın amacı postmenopozal kadınlarda OPG promoter bölgesindeki A163G ve
T245G polimorfizmleri ile kemik mineral yoğunluğu (KMY) arasındaki ilişkinin
değerlendirilmesidir.

Gereç ve Yöntemler: Çalışmaya primer postmenopozal osteoporozlu 109 gönüllü hasta ve
kontrol grubu olarak 85 sağlıklı kadın olacak şekilde toplam 194 kişi dahil
edilmiştir. L1, L4, total lomber vertebra (L1-4), boyun, kalça ve total kalça
KMY değerleri dual enerji X-ışını absorbsiyometrisi (DEXA) yöntemiyle
değerlendirilmiştir. OPG promoter
bölgesindeki A163G ve T245G polimorfizmleri polimeraz zincir reaksiyonu (PCR)
ve restriksiyon parça uzunluğu polimorfizmi (RFLP) kullanılarak belirlenmiştir.

Bulgular: Postmenopozal
kadınlarda genotip frekansları A163G polimorfizmi için AG+GG (%46,8), AA
(%53,2); T245G için GG+TG (%36,7), TT (%63,3) olarak kaydedilmiştir. Sağlıklı
kadınlara kıyasla, osteoporozlu kadınlar arasında AG+GG (p=
0,005)
ve GG+TG (p=0,049) genotipleri
belirgin şekilde daha yaygın bulunmuştur. Postmenopozal kadınlarda ve
kontrollerde sırasıyla T245G ve A163G polimorfizmleri için genotipler ile
lomber vertebra KMY değerleri arasında önemli bir ilişki olduğu saptanmıştır
(sırasıyla p
˂0.05, p˂0.05, p˂0.05 ve p˂0.05). T245G polimorfizmi için GG+TG genotipleri
TT genotipine kıyasla daha düşük KMY ile ilişkili bulunmuştur. Benzer şekilde,
A163G polimorfizmi için de AG+GG genotipleri AA genotipine kıyasla daha düşük KMY ile ilişkilendirilmiştir.







Sonuç: Bu çalışmada elde
edilen bulgular, OPG promoter bölgesindeki T245G ve A163G polimorfizmlerinin
KMY’nin genetik düzenlenmesine katkıda bulunabileceğini düşündürmektedir.
  Bu
bulgular, gelecekte yapılacak osteoporoz çalışmalarında OPG geninin rolü
araştırılırken yararlı olacaktır.

Kaynakça

  • 1. Stewart, T.L. and S.H. Ralston, Role of genetic factors in the pathogenesis of osteoporosis. J Endocrinol, 2000. 166(2): p. 235-45.2.
  • 2. Ozbas, H., S. Tutgun Onrat, and K. Ozdamar, Genetic and environmental factors in human osteoporosis. Mol Biol Rep, 2012. 39(12): p. 11289-96.
  • 3. Arko, B., et al., Association of the osteoprotegerin gene polymorphisms with bone mineral density in postmenopausal women. Maturitas, 2005. 51(3): p. 270-9.
  • 4. Albagha, O.M. and S.H. Ralston, Genetics and osteoporosis. Rheum Dis Clin North Am, 2006. 32(4): p. 659-80.
  • 5. Langdahl, B.L., et al., Polymorphisms in the osteoprotegerin gene are associated with osteoporotic fractures. J Bone Miner Res, 2002. 17(7): p. 1245-55. 6. Ralston, S.H., Genetics of o
  • 6. Ralston, S.H., Genetics of osteoporosis. Ann N Y Acad Sci, 2010. 1192: p. 181-9.
  • 7. Lee, Y.H., et al., Associations between osteoprotegerin polymorphisms and bone mineral density: a meta-analysis. Mol Biol Rep, 2010. 37(1): p. 227-34.
  • 8. Shen, L., et al., Association between osteoprotegerin genetic variants and bone mineral density in Chinese women. Int Immunopharmacol, 2013. 16(2): p. 275-8.
  • 9. Jorgensen, H.L., et al., Serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter region are related to peripheral measures of bone mass and fracture odds ratios. J Bone Miner Metab, 2004. 22(2): p. 132-8.
  • 10. Vidal, C., R. Formosa, and A. Xuereb-Anastasi, Functional polymorphisms within the TNFRSF11B (osteoprotegerin) gene increase the risk for low bone mineral density. J Mol Endocrinol, 2011. 47(3): p. 327-33.
  • 11. Soufi, M., et al., Osteoprotegerin gene polymorphisms in men with coronary artery disease. J Clin Endocrinol Metab, 2004. 89(8): p. 3764-8.
  • 12. Wang, Q., et al., The relationship between osteoprotegerin gene polymorphisms and bone mineral density in Chinese postmenopausal women. Int Immunopharmacol, 2013. 17(2): p. 404-7.
  • 13. Garcia-Unzueta, M.T., et al., Association of the 163A/G and 1181G/C osteoprotegerin polymorphism with bone mineral density. Horm Metab Res, 2008. 40(3): p. 219-24.
  • 14. Arko, B., et al., Sequence variations in the osteoprotegerin gene promoter in patients with postmenopausal osteoporosis. J Clin Endocrinol Metab, 2002. 87(9): p. 4080-4
  • 15. Cvijetic, S., et al., Osteoporosis and polymorphisms of osteoprotegerin gene in postmenopausal women - a pilot study. Reumatologia, 2016. 54(1): p. 10-3.
  • 16. Akker, M., et al., Investigation of insulin resistance gene polymorphisms in patients with differentiated thyroid cancer. Mol Biol Rep, 2014. 41(5): p. 3541-7.
  • 17. Zajickova, K., et al., Is A163G polymorphism in the osteoprotegerin gene associated with heel velocity of sound in postmenopausal women? Physiol Res, 2008. 57 Suppl 1: p. S153-7.
  • 18. Cheung, C.L., S.M. Xiao, and A.W. Kung, Genetic epidemiology of age-related osteoporosis and its clinical applications. Nat Rev Rheumatol, 2010. 6(9): p. 507-17.
  • 19. Hofbauer, L.C. and M. Schoppet, Osteoprotegerin gene polymorphism and the risk of osteoporosis and vascular disease. J Clin Endocrinol Metab, 2002. 87(9): p. 4078-9.
  • 20. Yu, F., et al., Association between osteoprotegerin genetic variants and osteoporosis in Chinese postmenopausal women. Endocr J, 2013. 60(12): p. 1303-7.
  • 21. Nguyen, T.V., J. Blangero, and J.A. Eisman, Genetic epidemiological approaches to the search for osteoporosis genes. J Bone Miner Res, 2000. 15(3): p. 392-401.
  • 22. Wynne, F., et al., Investigation of the genetic influence of the OPG, VDR (Fok1), and COLIA1 Sp1 polymorphisms on BMD in the Irish population. Calcif Tissue Int, 2002. 71(1): p. 26-35.
  • 23. Ueland, T., et al., No associations between OPG gene polymorphisms or serum levels and measures of osteoporosis in elderly Australian women. Bone, 2007. 40(1): p. 175-81.
  • 24. Wang, F., et al., Association analysis between g.18873C>T and g.27522G>A genetic polymorphisms of OPG and bone mineral density in Chinese postmenopausal women. Biomed Res Int, 2014. 2014: p. 320828.

Association analysis between A163G and T245G gene polymorphisms of osteoprotegerin and bone mineral density in Turkish postmenopausal women

Yıl 2018, Cilt: 2 Sayı: 3, 222 - 229, 30.12.2018

Öz

Objectives:

Osteoprotegerin (OPG) is a gene which is accepted as one of the leading factor causing osteoporosis. Evaluation of the relationship between bone mineral density (BMD) and two polymorphisms in the OPG promoter, namely A163G and T245G among postmenopausal women was the goal of this study.

 

Material and methods: A total of 194 women, 109 with postmenopausal osteoporosis and 85 healthy controls, were included in the study. Dual-energy X-ray absorptiometry was used to evaluate BMD of L1, L4, total lumbar spine (L1-4), neck, hip and total hip. A163G and T245G polymorphisms were determined by PCR and RFLP.

Results: The frequencies of genotypes were as follows: AG+GG (46.8%), AA (53.2%) for A163G and GG+TG (36.7%), TT (63.3%) for T245G. Compared to healthy women, remarkably more women with osteoporosis were found to have AG+GG (p=0.005) and GG+TG (p=0.049). Significant associations were observed between the genotypes and BMD of the lumbar spine for the T245G and A163G polymorphisms in postmenopausal women and controls (p˂0.05 for all). The GG+TG genotypes correlated with lower BMD compared to TT for T245G. Similarly, for A163G, the AG+GG genotypes were related to in smaller amounts BMD compared to AA.

Conclusion: The study findings indicate that genetic arrangement of BMD can be contributed by the  T245G and A163G polymorphisms in the OPG promoter. These results are expected to be beneficial for further studies investigating the role of OPG in osteoporosis.













 

Kaynakça

  • 1. Stewart, T.L. and S.H. Ralston, Role of genetic factors in the pathogenesis of osteoporosis. J Endocrinol, 2000. 166(2): p. 235-45.2.
  • 2. Ozbas, H., S. Tutgun Onrat, and K. Ozdamar, Genetic and environmental factors in human osteoporosis. Mol Biol Rep, 2012. 39(12): p. 11289-96.
  • 3. Arko, B., et al., Association of the osteoprotegerin gene polymorphisms with bone mineral density in postmenopausal women. Maturitas, 2005. 51(3): p. 270-9.
  • 4. Albagha, O.M. and S.H. Ralston, Genetics and osteoporosis. Rheum Dis Clin North Am, 2006. 32(4): p. 659-80.
  • 5. Langdahl, B.L., et al., Polymorphisms in the osteoprotegerin gene are associated with osteoporotic fractures. J Bone Miner Res, 2002. 17(7): p. 1245-55. 6. Ralston, S.H., Genetics of o
  • 6. Ralston, S.H., Genetics of osteoporosis. Ann N Y Acad Sci, 2010. 1192: p. 181-9.
  • 7. Lee, Y.H., et al., Associations between osteoprotegerin polymorphisms and bone mineral density: a meta-analysis. Mol Biol Rep, 2010. 37(1): p. 227-34.
  • 8. Shen, L., et al., Association between osteoprotegerin genetic variants and bone mineral density in Chinese women. Int Immunopharmacol, 2013. 16(2): p. 275-8.
  • 9. Jorgensen, H.L., et al., Serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter region are related to peripheral measures of bone mass and fracture odds ratios. J Bone Miner Metab, 2004. 22(2): p. 132-8.
  • 10. Vidal, C., R. Formosa, and A. Xuereb-Anastasi, Functional polymorphisms within the TNFRSF11B (osteoprotegerin) gene increase the risk for low bone mineral density. J Mol Endocrinol, 2011. 47(3): p. 327-33.
  • 11. Soufi, M., et al., Osteoprotegerin gene polymorphisms in men with coronary artery disease. J Clin Endocrinol Metab, 2004. 89(8): p. 3764-8.
  • 12. Wang, Q., et al., The relationship between osteoprotegerin gene polymorphisms and bone mineral density in Chinese postmenopausal women. Int Immunopharmacol, 2013. 17(2): p. 404-7.
  • 13. Garcia-Unzueta, M.T., et al., Association of the 163A/G and 1181G/C osteoprotegerin polymorphism with bone mineral density. Horm Metab Res, 2008. 40(3): p. 219-24.
  • 14. Arko, B., et al., Sequence variations in the osteoprotegerin gene promoter in patients with postmenopausal osteoporosis. J Clin Endocrinol Metab, 2002. 87(9): p. 4080-4
  • 15. Cvijetic, S., et al., Osteoporosis and polymorphisms of osteoprotegerin gene in postmenopausal women - a pilot study. Reumatologia, 2016. 54(1): p. 10-3.
  • 16. Akker, M., et al., Investigation of insulin resistance gene polymorphisms in patients with differentiated thyroid cancer. Mol Biol Rep, 2014. 41(5): p. 3541-7.
  • 17. Zajickova, K., et al., Is A163G polymorphism in the osteoprotegerin gene associated with heel velocity of sound in postmenopausal women? Physiol Res, 2008. 57 Suppl 1: p. S153-7.
  • 18. Cheung, C.L., S.M. Xiao, and A.W. Kung, Genetic epidemiology of age-related osteoporosis and its clinical applications. Nat Rev Rheumatol, 2010. 6(9): p. 507-17.
  • 19. Hofbauer, L.C. and M. Schoppet, Osteoprotegerin gene polymorphism and the risk of osteoporosis and vascular disease. J Clin Endocrinol Metab, 2002. 87(9): p. 4078-9.
  • 20. Yu, F., et al., Association between osteoprotegerin genetic variants and osteoporosis in Chinese postmenopausal women. Endocr J, 2013. 60(12): p. 1303-7.
  • 21. Nguyen, T.V., J. Blangero, and J.A. Eisman, Genetic epidemiological approaches to the search for osteoporosis genes. J Bone Miner Res, 2000. 15(3): p. 392-401.
  • 22. Wynne, F., et al., Investigation of the genetic influence of the OPG, VDR (Fok1), and COLIA1 Sp1 polymorphisms on BMD in the Irish population. Calcif Tissue Int, 2002. 71(1): p. 26-35.
  • 23. Ueland, T., et al., No associations between OPG gene polymorphisms or serum levels and measures of osteoporosis in elderly Australian women. Bone, 2007. 40(1): p. 175-81.
  • 24. Wang, F., et al., Association analysis between g.18873C>T and g.27522G>A genetic polymorphisms of OPG and bone mineral density in Chinese postmenopausal women. Biomed Res Int, 2014. 2014: p. 320828.
Toplam 24 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Bölüm Araştırma Makalesi
Yazarlar

Orkide Palabıyık 0000-0002-3488-3740

Ferda Ozdemır Bu kişi benim 0000-0003-1919-2586

Bucu Tokuc 0000-0002-5998-4070

Tammam Sıpahı Bu kişi benim 0000-0002-9471-6071

Derya Demırbag Kabayel Bu kişi benim 0000-0002-5331-1668

Yayımlanma Tarihi 30 Aralık 2018
Kabul Tarihi 30 Aralık 2018
Yayımlandığı Sayı Yıl 2018 Cilt: 2 Sayı: 3

Kaynak Göster

Vancouver Palabıyık O, Ozdemır F, Tokuc B, Sıpahı T, Demırbag Kabayel D. Association analysis between A163G and T245G gene polymorphisms of osteoprotegerin and bone mineral density in Turkish postmenopausal women. Med J West Black Sea. 2018;2(3):222-9.

Zonguldak Bülent Ecevit Üniversitesi Tıp Fakültesi’nin bilimsel yayım organıdır.

Ulusal ve uluslararası tüm kurum ve kişilere elektronik olarak ücretsiz ulaşmayı hedefleyen hakemli bir dergidir.

Dergi yılda üç kez olmak üzere Nisan, Ağustos ve Aralık aylarında yayımlanır.

Derginin yayım dili Türkçe ve İngilizcedir.