Background:Lumbar disc degeneration [LDD] is the main cause of low back pain, and is
a medical circumstance that poses a great load on the global health care system
with serious socioeconomic consequences. The aim of this study was to determine
the association of vitamin D receptors (VDR) gene Fok1 polymorphism, VDR
expression and vitamin D level with LDD susceptibility and severity in
Egyptians.Materials and methods: A total of unrelated 169 female patients with low back pain diagnosed as
having lumbar disc degeneration and 169 controls were enrolled in the study.
VDR Fok1 polymorphism was determined using restriction fragment length
polymorphism-polymerase chain reaction [PCR-RFLP]. VDR expression was measured by
reverse transcriptase PCR, while, serum levels of vitamin D were measured by high performance liquid chromatography [HPLC].Results:Subjects with VDR Fok1 ff genotype were significantly more likely to
developLDD in Egyptians and associated with multilevel disc degeneration and
disc herniation(adjusted OR=7.9, 95% CI= 2.3-26.6 and P = 0.01) and (adjusted OR=2.2,
95% CI= 1.6-
References
[1]
Juniper, M., Le, T.K. and Mladsi, D. (2009) The Epidemiology, Economic Burden, and Pharmacological Treatment of Chronic Low Back Pain in France, Germany, Italy, Spain and the UK: A Literature-Based Review. Expert Opinion on Pharmacotherapy, 10, 2581-2592. https://doi.org/10.1517/14656560903304063
[2]
Cheung, K.M., Karppinen, J., Chan, D., et al. (2009) Prevalence and Pattern of Lumbar Magnetic Resonance Imaging Changes in a Population Study of One Thousand Forty-Three Individuals. Spine, 34, 934-940.
https://doi.org/10.1097/BRS.0b013e3181a01b3f
[3]
Zhang, Y.G., Sun, Z., Zhang, Z., Liu, J. and Guo, X. (2009) Risk Factors for Lumbar Intervertebral Disc Herniation in Chinese Population: A Case-Control Study. Spine, 34, E918-E922. https://doi.org/10.1097/BRS.0b013e3181a3c2de
[4]
Zawilla, N.H., Darweesh, H., Mansour, N., et al. (2014) Matrix Metalloproteinase-3, Vitamin D Receptor Gene Polymorphisms, and Occupational Risk Factors in Lumbar Disc Degeneration. Journal of Occupational Rehabilitation, 24, 370-381.
https://doi.org/10.1007/s10926-013-9472-7
[5]
Kalichman, L. and Hunter, D.J. (2008) The Genetics of Intervertebral Disc Degeneration. Associated Genes. Joint Bone Spine, 75, 388-396.
https://doi.org/10.1016/j.jbspin.2007.11.002
[6]
Walter, B.A., Korecki, C.L., Purmessur, D., Roughley, P.J., Michalek, A.J. and Iatridis, J.C. (2011) Complex Loading Affects Intervertebral Disc Mechanics and Biology. Osteoarthritis and Cartilage, 19, 1011-1018.
https://doi.org/10.1016/j.joca.2011.04.005
[7]
Battie, M.C., Videman, T., Levalahti, E., Gill, K. and Kaprio, J. (2007) Heritability of Low Back Pain and the Role of Disc Degeneration. Pain, 131, 272-280.
https://doi.org/10.1016/j.pain.2007.01.010
[8]
Cantorna, M.T. and Mahon, B.D. (2004) Mounting Evidence for Vitamin D as an Environmental Factor Affecting Autoimmune Disease Prevalence. Experimental Biology and Medicine, 229, 1136-1142.
[9]
Videman, T., Leppavuori, J., Kaprio, J., Battie, M.C., Gibbons, L.E., et al. (1998) Intragenic Polymorphisms of the Vitamin D Receptor Gene Associated with Intervertebral Disc Degeneration. Spine, 23, 2477-2485.
https://doi.org/10.1097/00007632-199812010-00002
[10]
Uitterlinden, A.G., Fang, Y., van Meurs, J.B.J., Pols, H.A.P. and van Leeuwen, J.P.T.M. (2004) Genetics and Biology of Vitamin D Receptor Polymorphisms. Gene, 338, 143-156.
[11]
Carlberg, C. and Molnar, F. (2006) Detailed Molecular Understanding of Agonistic and Antagonistic Vitamin D Receptor Ligands. Current Topics in Medicinal Chemistry, 6, 1243-1253. https://doi.org/10.2174/156802606777864908
[12]
Mory, D.B., Rocco, E.R., Miranda, W.L., et al. (2009) Prevalence of Vitamin D Receptor Gene Polymorphisms FokI and BsmI in Brazilian Individuals with Type 1 Diabetes and Their Relation to Beta-Cell Autoimmunity and to Remaining Beta-Cell Function. Human Immunology, 70, 447-451.
https://doi.org/10.1016/j.humimm.2009.03.007
[13]
Vilarino, F.L., Bianco, B., Christofolini, D.M., et al. (2011) Analysis of VDR Gene Polymorphism Fok1 in Infertile Women with Endometriosis. Revista Brasileira de Ginecologia e Obstetrícia, 33, 65-69.
[14]
Eser, B., Cora, T., Eser, O., Kalkan, E., Haktanir, A., et al. (2010) Association of the Polymorphisms of Vitamin D Receptor and Aggrecan Genes with Degenerative Disc Disease. Genetic Testing and Molecular Biomarkers, 14, 313-317.
https://doi.org/10.1089/gtmb.2009.0202
[15]
Eskola, P.J., Kjaer, P., Daavittila, I.M., Solovieva, S., Okuloff, A., et al. (2010) Genetic Risk Factors of Disc Degeneration among 12 -14-Year-Old Danish Children: A Population Study. International Journal of Molecular Epidemiology and Genetics, 1, 158-165.
[16]
Kelempisioti, A., Eskola, P.J., Okuloff, A., Karjalainen, U., Takatalo, J., et al. (2011) Genetic Susceptibility of Intervertebral Disc Degeneration among Young Finnish Adults. BMC Medical Genetics, 12, 153. https://doi.org/10.1186/1471-2350-12-153
[17]
Wiktorin, C., Hjelm, E.W., Winkel, J. and Koster, M. (1996) Reproducibility of a Questionnaire for Assessment of Physical Load during Work and Leisure Time. Journal of Occupational & Environmental Medicine, 38, 190-201.
https://doi.org/10.1097/00043764-199602000-00017
[18]
Schneiderman, G., Flannigan, B., Kingston, S., Thomas, J., Dillin, W.H. and Watkins, R.G. (1987) Magnetic Resonance Imaging in the Diagnosis of Disc Degeneration: Correlation with Discography. Spine, 12, 276-281.
https://doi.org/10.1097/00007632-198704000-00016
[19]
Horst-Sikorska, W., Kalak, R., Wawrzyniak, A., et al. (2007) Association Analysis of the Polymorphisms of the VDR Gene with Bone Mineral Density and the Occurrence of Fractures. Journal of Bone and Mineral Metabolism, 25, 310-319.
https://doi.org/10.1007/s00774-007-0769-5
[20]
Cross, H.S., Bareis, P., Hofer, H., Bischof, M.G., Bajna, E., Kriwanek, S., Bonner, E. and Peterlik, M. (2001) 25-Hydroxyvitamin D[3]-1Alpha-Hydroxylase and Vitamin D Receptor Gene Expression in Human Colonic Mucosa Is Elevated during Early Cancerogenesis. Steroids, 66, 287-292.
[21]
Ursula, T., Ulla, H. and Ulf-Hakan, S. (2003) Determination of 25-Hydroxyvitamin D in Serum by HPLC and Immunoassay. Clinical Chemistry, 49, 1521-1524.
https://doi.org/10.1373/49.9.1521
[22]
Gilbertson, T.J. and Stryd, R.P. (1997) High-Performance Liquid Chromatographic Assay for 25-Hydroxyvitamin D3 in Plasma. Clinical Chemistry, 23, 1700-1704.
[23]
Skol, A.D., Scott, L.J., Abecasis, G.R. and Boehnke, M. (2006) Joint Analysis Is More Efficient than Replication-Based Analysis for Two-Stage Genome-Wide Association Studies. Nature Genetics, 38, 209-213. https://doi.org/10.1038/ng0306-390
[24]
Chan, W.C.W., Sze, K.L., Samartzis, D., Leung, V.Y.L. and Chan, D. (2011) Structure and Biology of the Intervertebral Disc in Health and Disease. Orthopedic Clinics of North America, 42, 447-464. https://doi.org/10.1016/j.ocl.2011.07.012
[25]
Samartzis, D., Karppinen, J., Mok, F., Fong, D.Y.T., Luk, K.D.K., et al. (2011) A Population-Based Study of Juvenile Disc Degeneration and Its Association with Overweight and Obesity, Low Back Pain, and Diminished Functional Status. Journal of Bone & Joint Surgery-American Volume, 93, 662-670.
https://doi.org/10.2106/JBJS.I.01568
[26]
Matsui, H., Terahata, N., Tsuji, H., Hirano, N. and Naruse, Y. (1992) Familial Predisposition and Clustering for Juvenile Lumbar Disc Herniation. Spine, 17, 1323-1328. https://doi.org/10.1097/00007632-199211000-00011
[27]
Colombini, A., Brayda-Bruno, M., Ferino, L., Lombardi, G., Maione, V., Banfi, G. and Cauci, S. (2015) Gender Differences in the VDR-FokI Polymorphism and Conventional Non-Genetic Risk Factors in Association with Lumbar Spine Pathologies in an Italian Case-Control Study. International Journal of Molecular Sciences, 16, 3722-3739. https://doi.org/10.3390/ijms16023722
[28]
Vieira, L., De Marchi, P., Santos, A., Christofolini, D., Barbosa, C., Fonseca, F., Bianco, B. and Rodrigues, L. (2014) Analysis of FokI Polymorphism of Vitamin D Receptor Gene in Intervertebral Disc Degeneration. Genetic Testing and Molecular Biomarkers, 18, 625-629.
[29]
Nunes, F.T.B., Conforti-Froes, N.D.T., Negrelli, W.F. and Sousa, D.R.S. (2007) Genetic and Environmental Factors Involved on Intervertebral Disc Degeneration. Acta Ortopédica Brasileira, 15, 9-13.
https://doi.org/10.1590/S1413-78522007000100002
[30]
Colombini, A., Brayda-Bruno, M., Lombardi, G., Croiset, S.J., Vrech, V., et al. (2014) 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, 9, e97027. https://doi.org/10.1371/journal.pone.0097027
[31]
Omair, A., Lie, B.A., Reikeras, O. and Brox, J.I. (2012) An Association Study of Interleukin 18 Receptor Genes [IL18R1 and IL18RAP] in Lumbar Disc Degeneration. The Open Orthopaedics Journal 6, 164-171.
https://doi.org/10.2174/1874325001206010164
[32]
Serrano, S.C., Villareal, D.G., Aguilar-Medina, M., et al. (2014) Genetic Polymorphisms of Interleukin-1 Alpha and the Vitamin D Receptor in Mexican Mestizo Patients with Intervertebral Disc Degeneration. International Journal of Genomics, 2014, Article ID: 302568.
[33]
Arai, H., Miyamoto, K., Taketani, Y., et al. (1997) A Vitamin D Receptor Gene Polymorphism in the Translation Initiation Codon: Effect on Protein Activity and Relation to Bone Mineral Density in Japanese Women. Journal of Bone and Mineral Research, 12, 915-921. https://doi.org/10.1359/jbmr.1997.12.6.915
[34]
Corvol, M.T., Dumontier, M.F., Tsagris, L., Lang, F. and Bourguignon, J. (1981) Cartilage and Vitamin D in Vitro [author’s transl]. Annales d’Endocrinologie, 42, 482-487.
[35]
Kawaguchi, Y., Kanamori, M., Ishihara, H., Ohmori, K., Matsui, H. and Kimura, T. (2002) The Association of Lumbar Disc Disease with Vitamin-D Receptor Gene Polymorphism. Journal of Bone & Joint Surgery-American Volume, 84, 2022-2028.
https://doi.org/10.2106/00004623-200211000-00018
[36]
Nejentsev, S., Godfrey, L., Snook, H., et al. (2004) Comparative High-Resolution Analysis of Linkage Disequilibrium and Tag Single Nucleotide Polymorphisms between Populations in the Vitamin D Receptor Gene. Human Molecular Genetics, 13, 1633-1639. https://doi.org/10.1093/hmg/ddh169
[37]
Stoker, G., Buchowski, J., Chen, C., Kim, H., Park, M.S. and Riew, K.D. (2013) Hypovitaminosis D and Cervical Disk Herniation among Adults Undergoing Spine Surgery. Global Spine Journal, 3, 231-236. https://doi.org/10.1055/s-0033-1354252
[38]
Lodh, M., Goswami, B., Mahajan, R.D., Sen, D., Jajodia, N. and Roy, A. (2015) Assessment of Vitamin D Status In Patients of Chronic Low Back Pain of Unknown Etiology. Indian Journal of Clinical Biochemistry, 30, 174-179.
https://doi.org/10.1007/s12291-014-0435-3
[39]
Shankar, H., Scarlett, J.A. and Abram, S.E. (2009) Anatomy and Pathophysiology of Intervertebral Disc Disease. Techniques in Regional Anesthesia & Pain Management, 13, 67-75. https://doi.org/10.1053/j.trap.2009.05.001
[40]
Shamji, M.F., Setton, L.A., Jarvis, W., So, S., Chen, J., Jing, L., Bullock, R., Isaacs, R.E., Brown, C. and Richardson, W.J. (2010) Proinflammatory Cytokine Expression Profile in Degenerated and Herniated Human Intervertebral Disc Tissues. Arthritis & Rheumatology, 62, 1974-1982.
