The Elevated BMI is Considerably Associated with IDD Rather than Polymorphic variations in Interleukin-1 and Vitamin D Receptor Genes: A Case-Control Study
BMI and IDD
Abstract
Intervertebral disc degeneration (IDD) is a musculoskeletal disorder and one of the major causes of low back pain leading to the disability with high economic repercussions worldwide. This study applied the candidate-gene approach to investigate the potential association of selected polymorphisms with IDD development in a Jordanian population. MRI-diagnosed IDD patients (N=155) and asymptomatic individuals as a control group (N=55). Whole blood samples for four variants in three genes (rs1800587 of IL-1α, rs1143634 of IL-1b and rs2228570 and rs731236 of VDR) were genotyped by PCR-RFLP. There was no significant association between the studied polymorphisms or their allelic frequency and the occurrence of IDD. However, the cohort presented a significant reverse association between rs1143634 C>T of the IL-1β gene and the occurrence of IDD (p< 0.0001). In addition; BMI showed a significant association with the IDD in the study population (p< 0.005). The current study was conceptualized based on the candidate-gene approach to investigate the role of inflammatory and metabolic genes, IL and VDR respectively, in the occurrence of IDD. While data presented in this study showed that polymorphisms in these genes were not associated with IDD of the cohort investigated, elevated BMI, as a measure of obesity strongly associated with IDD. Investigating potential roles of other structural genes, such as col-IX and aggrecan (ACAN), in IDD and considering a GWAS to elucidate a genomically global look at the basis of IDD development would be of considerable impact on our understanding of IDD.
References
2. Zhao J, Yang M, Shao J, Bai Y, Li M. Association Between VDR FokI Polymorphism and Intervertebral Disk Degeneration. Genomics Proteomics Bioinformatics. 2015;13(6):371-6.
3. Guiot BH, Fessler RG. Molecular biology of degenerative disc disease. Neurosurgery. 2000;47(5):1034-40.
4. Cervin Serrano S, Gonzalez Villareal D, Aguilar-Medina M, 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.
5. Patino MG, Neiders ME, Andreana S, Noble B, Cohen RE. Collagen: an overview. Implant dentistry. 2002;11(3):280-5.
6. Antoniou J, Steffen T, Nelson F, et al. The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration. J Clin Invest. 1996;98(4):996-1003.
7. Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it? Spine (Phila Pa 1976). 2006;31(18):2151-61.
8. Battie MC, Videman T, Parent E. Lumbar disc degeneration: epidemiology and genetic influences. Spine (Phila Pa 1976). 2004;29(23):2679-90.
9. Urban JP, Roberts S. Degeneration of the intervertebral disc. Arthritis Res Ther. 2003;5(3):120-30.
10. Videman T, Saarela J, Kaprio J, et al. Associations of 25 structural, degradative, and inflammatory candidate genes with lumbar disc desiccation, bulging, and height narrowing. Arthritis Rheum. 2009;60(2):470-81.
11. Cheung KM, Chan D, Karppinen J, et al. Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in a Chinese population. Spine (Phila Pa 1976). 2006;31(10):1143-8.
12. Kawaguchi Y, Kanamori M, Ishihara H, Ohmori K, Matsui H, Kimura T. The association of lumbar disc disease with vitamin-D receptor gene polymorphism. J Bone Joint Surg Am. 2002;84-A(11):2022-8.
13. Uitterlinden AG, Burger H, Huang Q, et al. Vitamin D receptor genotype is associated with radiographic osteoarthritis at the knee. J Clin Invest. 1997;100(2):259-63.
14. Wood RJ, Fleet JC. The genetics of osteoporosis: vitamin D receptor polymorphisms. Annu Rev Nutr. 1998;18:233-58.
15. Pociot F, Molvig J, Wogensen L, Worsaae H, Nerup J. A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro. Eur J Clin Invest. 1992;22(6):396-402.
16. Noponen-Hietala N, Virtanen I, Karttunen R, et al. Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica. Pain. 2005;114(1-2):186-94.
17. Videman T, Leppavuori J, Kaprio J, et al. Intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration. Spine (Phila Pa 1976). 1998;23(23):2477-85.
18. Uitterlinden AG, Fang Y, Bergink AP, van Meurs JB, van Leeuwen HP, Pols HA. The role of vitamin D receptor gene polymorphisms in bone biology. Mol Cell Endocrinol. 2002;197(1-2):15-21.
19. Morrison NA, Qi JC, Tokita A, et al. Prediction of bone density from vitamin D receptor alleles. Nature. 1994;367(6460):284-7.
20. Le Maitre CL, Freemont AJ, Hoyland JA. The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Res Ther. 2005;7(4):R732-45.
21. Paz Aparicio J, Fernandez Bances I, Lopez-Anglada Fernandez E, et al. The IL-1beta (+3953 T/C) gene polymorphism associates to symptomatic lumbar disc herniation. Eur Spine J. 2011;20 Suppl 3:383-9.
22. Wang Z, Qu Z, Fu C, et al. Interleukin 1 Polymorphisms Contribute to Intervertebral Disc Degeneration Risk: A Meta-Analysis. PLoS One. 2016;11(6):e0156412.
23. Eser B, Cora T, Eser O, et al. Association of the polymorphisms of vitamin D receptor and aggrecan genes with degenerative disc disease. Genet Test Mol Biomarkers. 2010;14(3):313-7.
24. Kepler CK, Ponnappan RK, Tannoury CA, Risbud MV, Anderson DG. The molecular basis of intervertebral disc degeneration. Spine J. 2013;13(3):318-30.
25. Kelempisioti A, Eskola PJ, Okuloff A, et al. Genetic susceptibility of intervertebral disc degeneration among young Finnish adults. BMC Med Genet. 2011;12:153.
26. Solovieva S, Kouhia S, Leino-Arjas P, et al. Interleukin 1 polymorphisms and intervertebral disc degeneration. Epidemiology. 2004;15(5):626-33.
27. Eskola PJ, Kjaer P, Daavittila IM, 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(2):158-65.
28. Brinjikji W, Luetmer PH, Comstock B, et al. Systematic literature review of imaging features of spinal degeneration in asymptomatic populations. American Journal of Neuroradiology. 2015;36(4):811-6.
29. Wang C, McArdle E, Fenty M, et al. Validation of Sodium MRI of Intervertebral Disc. Spine. 2010;35(5):505.
30. Karppinen J, Solovieva S, Luoma K, Raininko R, Leino-Arjas P, Riihimaki H. Modic changes and interleukin 1 gene locus polymorphisms in occupational cohort of middle-aged men. Eur Spine J. 2009;18(12):1963-70.
31. Eskola PJ, Lemmela S, Kjaer P, et al. Genetic association studies in lumbar disc degeneration: a systematic review. PLoS One. 2012;7(11):e49995.
32. Solovieva S, Lohiniva J, Leino-Arjas P, et al. Intervertebral disc degeneration in relation to the COL9A3 and the IL-1ss gene polymorphisms. Eur Spine J. 2006;15(5):613-9.
33. Samartzis D, Karppinen J, Chan D, Luk KD, Cheung KM. The association of lumbar intervertebral disc degeneration on magnetic resonance imaging with body mass index in overweight and obese adults: a population‐based study. Arthritis & Rheumatism. 2012;64(5):1488-96.
34. Hangai M, Kaneoka K, Kuno S, et al. Factors associated with lumbar intervertebral disc degeneration in the elderly. The spine journal. 2008;8(5):732-40.
35. Li Z, Shen J, Wu WKK, et al. Leptin induces cyclin D1 expression and proliferation of human nucleus pulposus cells via JAK/STAT, PI3K/Akt and MEK/ERK pathways. PloS one. 2012;7(12):e53176.
36. Segar AH, Fairbank JC, Urban J. Leptin and the intervertebral disc: A biochemical link exists between obesity, intervertebral disc degeneration and low back pain—an in vitro study in a bovine model. European Spine Journal. 2019;28(2):214-23.
37. Zhao C-Q, Liu D, Li H, Jiang L-S, Dai L-Y. Expression of leptin and its functional receptor on disc cells: contribution to cell proliferation. Spine. 2008;33(23):E858-E64.
Copyright (c) 2020 Mazhar Salim Al Zoubi
This work is licensed under a Creative Commons Attribution 4.0 International License.
The published articles will be distributed under the Creative Commons Attribution 4.0 International License (CC BY). It is allowed to copy and redistribute the material in any medium or format, and remix, transform, and build upon it for any purpose, even commercially, as long as appropriate credit is given to the original author(s), a link to the license is provided and it is indicated if changes were made. Users are required to provide full bibliographic description of the original publication (authors, article title, journal title, volume, issue, pages), as well as its DOI code. In electronic publishing, users are also required to link the content with both the original article published in Journal of Medical Biochemistry and the licence used.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.