Lomber Disk Hernisi Tanısı Konan Türk Hastalarda Vitamin D Reseptör (VDR) Gen Polimorfizmlerinin Araştırılması

Year 2019, Volume: 9 Issue: 3, 93 - 98, 01.12.2019

Bahar Toptaş Hekimoğlu Hakan Eraltan Hidayet Sarı Mehmet Tolgahan Hakan Dilara Sönmez Ümit Zeybek Cem Horozoğlu Arzu Ergen İlhan Yaylım

Abstract

Amaç: Lomber disk hernisi (LDH) yaygın bir dejeneratif hastalıktır. D vitamini yolu ile hastalığın etyopatogenezi arasında olası bir ilişkinin varlığı çalışmalarda tam olarak gösterilememiştir. Bu çalışmada LDH hastalarında D vitamini düzeyini etkilediği bilinen VDR polimorfizmlerini araştırdık.

Gereç ve Yöntem: TaqI (rs731236) ve Fok-I (rs2228570) polimorfizmleri 72 LDH hasta ve 81 sağlıklı kontrol örneğinde polimeraz zincir reaksiyonu- restriksiyon fragman uzunluk polimorfizmi (PCR-RFLP) yöntemi kullanılarak incelendi.

Bulgular: Elde edilen bulguların değerlendirilmesi sonrası VDR Taq-I Tt genotipine LDH hastalarında görülme sıklığı kontrollerden anlamlı olarak yüksek olduğu ve Taq-I Tt genotip ve t alel taşıyıcılarının LDH vakaları için yüksek risk taşıyıcısı olduğu tespit edildi, sırasıyla; p=0,002, OR: 1,688,% 95CI: 1,206-2,360; p=0,006, OR: 1,420,% 95CI: 1,104-1,825. VDR Fok-I genotipleri LDH ve kontrol vakaları arasında değerledirildiğinde anlamlı farklılık gözlemlenmemiştir (p=0,079). Ancak, Ff genotipi ve f allel taşıyıcıları LDH hastaları için diğer genotiplere göre daha yüksek bir risk taşımaktadır. Sırasıyla; p=0,025, OR: 1,594, %95 CI: 1,052-2,414; p=0,037, OR: 1,514, %95 CI: 1,019-2,250.

Sonuç: Çalışmamız, LDH'li hastaların belirli alt grupları için genetik risk faktörlerinin tanımlanmasına katkıda bulunmaktadır ve genetik biyobelirteçlerin hastaların ayrıntılı klinik değerlendirmesine katkısının önemini vurgulamaktadır.

Cite this article as: Toptaş Hekimoğlu B, Eraltan H, Sarı H, Hakan MT, Sönmez D, Horozoğlu C, et al. Investigation of The Vitamin D Receptor (VDR) Gene Polymorphisms in Lumbar Disc Herniation in Turkish Patients. Experimed 2019; 9(3): 93-8.

Keywords

D vitamini reseptörü, polimorfizm, lomber disk hernisi

Investigation of The Vitamin D Receptor (VDR) Gene Polymorphisms in Lumbar Disc Herniation in Turkish Patients

Abstract

Objective: Lumbar disc herniation (LDH) is a common degenerative disease. It is still not clear if there is a possible association between the vitamin D pathway and the etiopathogenesis of the disease. In this study, we investigated certain VDR polymorphisms which are known to affect vitamin D levels in patients with lumbar disc herniation.

Material and Method: TaqI (rs731236) and Fok-I (rs2228570) polymorphisms were studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 72 LDH patients and 81 healthy controls.

Results: After evaluation of our results, the frequency of LDH patients who have VDR Taq-I Tt genotype was significantly higher than the controls and carriers of Taq-I Tt genotype and t allele who had an increased risk for lumbar disc hernia cases, respectively p=0.002, OR:1.688, 95%CI:1.206-2.360; p=0.006, OR:1.420, 95%CI:1.104-1.825. VDR Fok-I genotypes did not differ significantly between lumbar disc herniation and control cases. (p=0.079). But, Ff genotype and f allele carriers had a higher risk for lumbar disk hernia than those with other genotypes, respectively p=0.025, OR:1.594, 95%CI:1.052-2.414; p=0.037, OR:1.514, 95%CI:1.019-2.250.

Conclusion: Our study contributes to the identification of genetic risk factors for specific subgroups of patients with LDH, and emphasizes the contribution of these biomarkers to the detailed clinical evaluation of patients with genetic biomarkers.

Cite this article as: Toptaş Hekimoğlu B, Eraltan H, Sarı H, Hakan MT, Sönmez D, Horozoğlu C, et al. Investigation of The Vitamin D Receptor (VDR) Gene Polymorphisms in Lumbar Disc Herniation in Turkish Patients. Experimed 2019; 9(3): 93-8.

Keywords

Vitamin D receptor, polymorphism, lumbar disc herniation

References

• 1. Zhang Y, Sun Z, Liu J, Guo X. Advances in susceptibility genetics of intervertebral degenerative disc disease. Int J Biol Sci 2008; 4: 283-90. [CrossRef] 2. Paesold G, Nerlich AG, Boos N. Biological treatment strategies for disc degeneration: potentials and shortcomings. Eur Spine J 2007; 16: 447-68. [CrossRef] 3. Martirosyan NL, Patel AA, Carotenuto A, Kalani MYS, Belykh E, Walker CT, et al. Genetic Alterations in Intervertebral Disc Disease. Front Surg 2016; 3: 59. eCollection 2016. [CrossRef] 4. Colombini A, Cauci S, Lombardi G, Lanteri P, Croiset S, Brayda-Bruno M, et al. Relationship between vitamin D receptor gene (VDR) polymorphisms, vitamin D status, osteoarthritis and intervertebral disc degeneration. J Steroid Biochem Mol Biol 2013; 138: 24-40. [CrossRef] 5. Eskola PJ, Lemmelä S, Kjaer P, Solovieva S, Männikkö M, Tommerup N, et al. Genetic association studies in lumbar disc degeneration: a systematic review. PLoS One 2012; 7: e49995. doi: 10.1371/journal.pone.0049995. [CrossRef] 6. Zawilla NH, Darweesh H, Mansour N, Helal S, Taha FM, Awadallah M, et al. Matrix metalloproteinase-3, vitamin D receptor gene polymorphisms, and occupational risk factors in lumbar disc degeneration. J Occup Rehabil 2014; 24: 370-81. [CrossRef] 7. Taha MM, Sabbah NA, Rezk NA, Mansour H. Vitamin D Receptor Expression in Lumbar Disc Degeneration Patients. Open J Mod Neurosurg 2017; 7: 19-33. [CrossRef] 8. Kalichman L, Hunter DJ. The genetics of intervertebral disc degeneration.Familial predisposition and heritability estimation. Joint Bone Spine 2008; 75: 383-7. [CrossRef] 9. Vuolo L, Di Somma C, Faggiano A, Colao A. Vitamin D and cancer. Front Endocrinol (Lausanne) 2012; 3: doi: 10.3389/fendo.2012.00058. eCollection 2012. [CrossRef] 10. Mittal RD, Manchanda PK, Bhat S, Bid HK. Association of vitamin-D receptor (Fok-I) gene polymorphism with bladder cancer in an Indian population. BJU Int 2007; 99: 933-7. [CrossRef] 11. Amizuka N, Kwan MY, Goltzman D, Ozawa H, White JH. Vitamin D3 differentially regulates parathyroid hormone/parathyroid hormone-related peptide receptor expression in bone and cartilage. J Clin Invest 1999; 103: 373-81. [CrossRef] 12. Colombini A, Brayda-Bruno M, Lombardi G, Croiset SJ, Vrech V, Maione V, et al. FokI polymorphism in the vitamin D receptor gene (VDR) and its association with lumbar spine pathologies in the Italian population: a case-control study. PLoS One 2014; 9: e97027. doi: 10.1371/journal.pone.0097027. eCollection 2014. [CrossRef] 13. Vieira LA, De Marchi PL, dos Santos AA, Christofolini DM, Barbosa CP, Fonseca FLA, et al. Analysis of FokI polymorphism of vitamin D receptor gene in intervertebral disc degeneration. Genet Test Mol Biomarkers 2014; 18: 625-9. [CrossRef] 14. Eser B, Cora T, Eser O, Kalkan E, Haktanır A, Erdogan MO, et al. Association of the polymorphisms of vitamin D receptor and aggrecan genes with degenerative disc disease. Genet Test Mol Biomarkers 2010; 14: 313-7. [CrossRef] 15. Eskola PJ, Kjaer P, Daavittila IM, Solovieva S, Okuloff A, Sorensen JS, et al. Genetic risk factors of disc degeneration among 12-14-year-old Danish children: a population study. Int J Mol Epidemiol Genet 2010; 1: 158-65. 16. Bhanushali AA1, Lajpal N, Kulkarni SS, Chavan SS, Bagadi SS, Das BR. Frequency of fokI and taqI polymorphism of vitamin D receptor gene in Indian population and its association with 25-hydroxyvitamin D levels. Indian J Hum Genet 2009; 15: 108-13. [CrossRef] 17. Xu G, Mei Q, Zhou D, Wu J, Han L. Vitamin D receptor gene and aggrecan gene polymorphisms and the risk of intervertebral disc degeneration - a meta-analysis. PLoS One 2012; 7: e50243. doi: 10.1371/journal.pone.0050243. [CrossRef] 18. Toktaş ZO, Ekşi MŞ, Yılmaz B, Demir MK, Özgen S, Kılıç T, et al. Association of collagen I, IX and vitamin D receptor gene polymorphisms with radiological severity of intervertebral disc degeneration in Southern European Ancestor. Eur Spine J 2015; 24: 2432-41. [CrossRef] 19. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215. [CrossRef] 20. Toptaş B, Kafadar AM, Cacina C, Turan S, Yurdum LM, Yiğitbaşı N, et al. The vitamin D receptor (VDR) gene polymorphisms in Turkish brain cancer patients. Biomed Res Int 2013; 2013: 295791. doi: 10.1155/2013/295791. [CrossRef] 21. Colombini A, Brayda-Bruno M, Lombardi G, Croiset SJ, Vrech V, Maione V, et al. FokI polymorphism in the vitamin D receptor gene (VDR) and its association with lumbar spine pathologies in the Italian population: a case-control study. PLoS One 2014; 9: e97027. doi: 10.1371/journal.pone.0097027. eCollection 2014. [CrossRef] 22. Colombini A, Lanteri P, Lombardi G, Grasso D, Recordati C, Lovi A, et al. Metabolic effects of vitamin D active metabolites in monolayer and micromass cultures of nucleus pulposus and annulus fibrosus cells isolated from human intervertebral disc. Int J Biochem Cell Biol 2012; 44: 1019-30. [CrossRef] 23. Rajasekaran S, Kanna RM, Senthil N, Raveendran M, Ranjani V, Cheung KMC, et al. Genetic susceptibility of lumbar degenerative disc disease in young Indian adults. Eur Spine J 2015; 24:1969-75. [CrossRef] 24. Yaylım-Eraltan İ, Arzu Ergen H, Arıkan S, Okay E, Öztürk O, Bayrak S, et al. Investigation of the VDR gene polymorphisms association with susceptibility to colorectal cancer. Cell Biochem Funct 2007; 25: 731-7. [CrossRef] 25. Neyestani TR, Djazayery A, Shab-Bidar S, Eshraghian MR, Kalayi A, Shariatzadeh N, et al. Vitamin D Receptor Fok-I polymorphism modulates diabetic host response to vitamin D intake: need for a nutrigenetic approach. Diabetes Care 2013; 36: 550-6. [CrossRef] 26. Omair A, Lie BA, Reikeras O, Brox JI. An Association Study of Interleukin 18 Receptor Genes (IL18R1 and IL18RAP) in Lumbar Disc Degeneration. Open Orthop J 2012; 6: 164-71. [CrossRef] 27. Videman T, Leppävuori J, Kaprio J, Battié MC, Gibbons LE, Peltonen L, et al. Intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration. Spine (Phila Pa 1976) 1998; 23: 2477-85. [CrossRef] 28. Cervin Serrano S, González Villareal D, Aguilar-Medina M, Romero-Navarro JG, Romero Quintana JG, Arámbula Meraz E, et al. Genetic polymorphisms of interleukin-1 alpha and the vitamin d receptor in mexican mestizo patients with intervertebral disc degeneration. Int J Genomics 2014; 2014: 302568. doi: 10.1155/2014/302568. [CrossRef] 29. Cauci S, Migliozzi F, Trombetta CS, Venuto I, Saccheri P, Travan L, et al. Low back pain and FokI (rs2228570) polymorphism of vitamin D receptor in athletes. BMC Sports Sci Med Rehabil 2017 9: 4. doi: 10.1186/s13102-017-0069-x. eCollection 2017. [CrossRef] 30. Zhao J, Yang M, Shao J, Bai Y, Li M. Association Between VDR FokI Polymorphism and Intervertebral Disk Degeneration. Genomics Proteomics Bioinformatics 2015; 13: 371-6. [CrossRef]