Vitamin D receptor gene variants contribute to hip and knee osteoarthritis susceptibility

Authors

  • Vladimir Vranić 1. Clinic for Orthopedic Surgery and Traumatology, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia; 2. Medical Faculty of the Military Medical Academy, University of Defense, Belgrade, Serbia https://orcid.org/0000-0003-4625-0155
  • Katarina Zeljić Faculty of Biology, University of Belgrade, Studentski trg 3, 11000 Belgrade, Serbia https://orcid.org/0000-0002-6545-8616
  • Debora Štefik Institute for Medical Research, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia https://orcid.org/0000-0001-6610-4812
  • Nemanja Ivković Institute for Medical Research, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia https://orcid.org/0000-0001-8982-8848
  • Džihan Abazović Emergency Medical Center of Montenegro, Vaka Djurovića bb, 81000, Podgorica, Montenegro https://orcid.org/0000-0002-7676-458X
  • Nebojša Arsenijević Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia https://orcid.org/0000-0002-2107-3490
  • Danilo Vojvodić Institute for Medical Research, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia https://orcid.org/0000-0001-9308-3076
  • Gordana Šupić 1. Medical Faculty of the Military Medical Academy, University of Defense, Belgrade, Serbia; 2. Institute for Medical Research, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia

DOI:

https://doi.org/10.2298/ABS210329019V

Keywords:

Vitamin D, Vitamin D Receptor, Genetic polymorphisms, Osteoarthritis, VDR gene

Abstract

Paper description:

  • Vitamin D receptor (VDR) gene polymorphisms could play a significant role in susceptibility to osteoarthritis (OA), the most common degenerative joint disorder in humans.
  • VDR gene variants FokI, TaqI, ApaI and EcoRV were genotyped using TaqMan based Real-Time PCR in 94 OA patients and 100 healthy controls.
  • VDR FokI and TaqI genetic variants contribute to osteoarthritis susceptibility, occurrence of persistent pain and potentially to joint-specific OA risk.
  • Future directions could include supplementation according to VDR polymorphisms and serum vitamin D status to potentially delay OA onset, slow down its progression and reduce pain in OA patients.

Abstract: Vitamin D receptor (VDR) gene polymorphisms could play a significant role in the susceptibility and pathogenesis of osteoarthritis (OA), the most common degenerative joint disorder in humans. The current study involved 94 OA patients and 100 healthy, asymptomatic controls. VDR variants FokI (rs2228570), TaqI (rs731236), ApaI (rs7975232) and EcoRV (rs4516035) were genotyped using TaqMan-based real-time PCR. Adjusted odds ratio (OR) analysis showed that VDR TaqI and FokI polymorphisms are significantly associated with susceptibility to OA (OR=1.986, P=0.001 and OR=1.561, P=0.017, respectively). Joint-specific analysis showed that the VDR TaqI polymorphism was associated with risk of hip OA (OR=1.930, P=0.005) and knee OA (OR=1.916, P=0.028), while the VDR FokI polymorphism was associated with higher risk of knee OA (OR=2.117, P=0.012). VDR TaqI and FokI polymorphisms are associated with the occurrence of persistent pain (P=0.005 and P=0.027, respectively), while ApaI was associated with a family history of OA (p=0.004). The VDR FokI and TaqI genetic variants significantly contribute to osteoarthritis susceptibility, the occurrence of persistent pain, and potentially to joint-specific OA risk.

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References

GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388(10053):1545-602. https://doi.org/10.3410/f.731220250.793569875

Valdes AM, Spector TD. Genetic epidemiology of hip and knee osteoarthritis. Nat Rev Rheumatol. 2011;7(1):23-32.

Knapik JJ, Pope R, Orr R, Schram B. Osteoarthritis: Pathophysiology, Prevalence, Risk Factors, and Exercise for Reducing Pain and Disability. J Spec Oper Med. 2018;18(3):94-102.

Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Clin Geriatr Med. 2010;26(3):355-69.

Lanyon P, Muir K, Doherty S, Doherty M. Assessment of a genetic contribution to osteoarthritis of the hip: sibling study. BMJ. 2000;321(7270):1179-83. https://doi.org/10.1136/bmj.321.7270.1179

Mabey T, Honsawek S. Role of Vitamin D in Osteoarthritis: Molecular, Cellular, and Clinical Perspectives. Int J Endocrinol. 2015;2015:383918.

van Etten E, Verlinden L, Giulietti A, Ramos-Lopez E, Branisteanu DD, Ferreira GB, Overbergh L, Verstuyf A, Bouillon R, Roep BO, Badenhoop K, Mathieu C. The vitamin D receptor gene FokI polymorphism: functional impact on the immune system. Eur J Immunol. 2007;37(2):395-405. https://doi.org/10.1002/eji.200636043

Bagheri-Hosseinabadi Z, Imani D, Yousefi H, Abbasifard M. Vitamin D receptor (VDR) gene polymorphism and risk of rheumatoid arthritis (RA): systematic review and meta-analysis. Clin Rheumatol. 2020;39(12):3555-69. https://doi.org/10.1007/s10067-020-05143-y

Chen L, Zhao S, Niu F, Bi GB. Association between vitamin D receptor gene polymorphisms and intervertebral disc degeneration: A meta-analysis. J Orthopaedic Sci. 2017;22(2):184-9. https://doi.org/10.1016/j.jos.2016.11.009

Davis CD, Milner JA. Nutrigenomics, Vitamin D and Cancer Prevention. J Nutr Nutr. 2011;4(1):1-11.

Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP. Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004;338(2):143-56. https://doi.org/10.1016/j.gene.2004.05.014

Keen RW, Hart DJ, Lanchbury JS, Spector TD. Association of early osteoarthritis of the knee with a Taq I polymorphism of the vitamin D receptor gene. Arthritis Rheum. 1997;40(8):1444-9. https://doi.org/10.1002/art.1780400812

Uitterlinden AG, Burger H, Huang Q, Odding E, Duijn CM, Hofman A, Birkenhäger JC, van Leeuwen JP, Pols HA. Vitamin D receptor genotype is associated with radiographic osteoarthritis at the knee. J Clin Invest. 1997;100(2):259-63. https://doi.org/10.1172/jci119530

Yilmaz AD, Yazicioglu D, Tüzüner Öncül AM, Yilmaz E, Ereş G. Vitamin D receptor gene polymorphisms (Apa1 and Taq1) in temporomandibular joint internal derangement/osteoarthritis in a group of Turkish patients. Mol Biol Rep. 2018;45(6):1839-48. https://doi.org/10.1007/s11033-018-4330-5

González-Huerta NC, Borgonio-Cuadra VM, Morales-Hernández E, Duarte-Salazar C, Miranda-Duarte A. Vitamin D receptor gene polymorphisms and susceptibility for primary osteoarthritis of the knee in a Latin American population. Adv Rheumatol Lond Engl. 2018;58(1):6. https://doi.org/10.1186/s42358-018-0002-3

Ghaly MS, Badra DI, Dessouki O, Elmaraghy NN, Hassan R. Vitamin D receptor Fok1 & Bsm 1 Gene Polymorphisms in Systemic Lupus Erythematosus and Osteoarthritis: Autoimmune Inflammatory versus Degenerative Model. Egypt J Immunol. 2017;24(2):151-64.

Mukhtar M, Sheikh N, Suqaina SK, Batool A, Fatima N, Mehmood R, Nazir S. Vitamin D Receptor Gene Polymorphism: An Important Predictor of Arthritis Development. Biomed Res Int. 2019;2019:8326246. https://doi.org/10.1155/2019/8326246

Zhu ZH, Jin XZ, Zhang W, Chen M, Ye DQ, Zhai Y, Dong FL, Shen CL, Ding C. Associations between vitamin D receptor gene polymorphisms and osteoarthritis: an updated meta-analysis. Rheumatol Oxf Engl. 2014;53(6):998-1008. https://doi.org/10.1093/rheumatology/ket418

Liu H, He H, Li S, Yang L, Wang P, Liu C, Wei X, Wu T, He C. Vitamin D receptor gene polymorphisms and risk of osteoarthritis: a meta-analysis. Exp Biol Med Maywood NJ. 2014;239(5):559-67. https://doi.org/10.1177/1535370213514920

Lee YH, Woo JH, Choi SJ, Ji JD, Song GG. Vitamin D receptor TaqI, BsmI and ApaI polymorphisms and osteoarthritis susceptibility: a meta-analysis. Joint Bone Spine. 2009;76(2):156-61. https://doi.org/10.1016/j.jbspin.2008.06.011

Solovieva S, Hirvonen A, Siivola P, Vehmas T, Luoma K, Riihimäki H, Leino-Arjas P. Vitamin D receptor gene polymorphisms and susceptibility of hand osteoarthritis in Finnish women. Arthritis Res Ther. 2006;8(1):R20. https://doi.org/10.1186/ar1874

Li HM, Liu Y, Zhang RJ, Ding JY, Shen CL. Vitamin D receptor gene polymorphisms and osteoarthritis: a meta-analysis. Rheumatology. 2021;60(2):538-48. https://doi.org/10.1093/rheumatology/keaa644

Valdes AM, Hart DJ, Jones KA, Surdulescu G, Swarbrick P, Doyle DV, Schafer AJ, Spector TD. Association study of candidate genes for the prevalence and progression of knee osteoarthritis. Arthritis Rheum. 2004;50(8):2497-507. https://doi.org/10.1002/art.20443

Muraki S, Dennison E, Jameson K, Boucher BJ, Akune T, Yoshimura N, Judge A, Arden NK, Javaid K, Cooper C. Association of vitamin D status with knee pain and radiographic knee osteoarthritis. Osteoarthritis Cartilage. 2011;19(11):1301-6. https://doi.org/10.1016/j.joca.2011.07.017

Reynard LN, Loughlin J. The genetics and functional analysis of primary osteoarthritis susceptibility. Expert Rev Mol Med. 2013;15:e2. https://doi.org/10.1017/erm.2013.4

Xu Y, Barter MJ, Swan DC, Rankin KS, Rowan AD, Santibanez-Koref M, Loughlin J, Young DA. Identification of the pathogenic pathways in osteoarthritic hip cartilage: commonality and discord between hip and knee OA. Osteoarthritis Cartilage. 2012;20(9):1029-38. https://doi.org/10.1016/j.joca.2012.05.006

Karlsson C, Dehne T, Lindahl A, Brittberg M, Pruss A, Sittinger M, Ringe J. Genome-wide expression profiling reveals new candidate genes associated with osteoarthritis. Osteoarthritis Cartilage. 2010;18(4):581-92. https://doi.org/10.1016/j.joca.2009.12.002

Lastlett LL, Quinn S, Burgess JR, Parameswaran V, Winzenberg TM, Jones G, et al. Moderate vitamin D deficiency is associated with changes in knee and hip pain in older adults: a 5‐year longitudinal study. Ann Rheum Dis. 2014;73:697-703. https://doi.org/10.1136/annrheumdis-2012-202831

Wu Z, Malihi Z, Stewart AW, Lawes CM, Scragg R. The association between vitamin D concentration and pain: a systematic review and meta‐analysis. Public Health Nutr. 2018;21:2022-37. https://doi.org/10.1017/s1368980018000551

Shipton EA, Shipton EE. Vitamin D and Pain: Vitamin D and Its Role in the Aetiology and Maintenance of Chronic Pain States and Associated Comorbidities. Pain Res Treat. 2015;2015:904967. https://doi.org/10.1155/2015/904967

Cao Y, Winzenberg T, Nguo K, Lin J, Jones G, Ding C. Association between serum levels of 25-hydroxyvitamin D and osteoarthritis: a systematic review. Rheumatol Oxf Engl. 2013;52(7):1323-34. https://doi.org/10.1093/rheumatology/ket132

Huhtakangas JA, Veijola J, Turunen S, Karjalainen A, Valkealahti M, Nousiainen T, Yli-Luukko S, Vuolteenaho O, Lehenkari P. 1,25(OH)2D3 and calcipotriol, its hypocalcemic analog, exert a long-lasting anti-inflammatory and anti-proliferative effect in synoviocytes cultured from patients with rheumatoid arthritis and osteoarthritis. J Steroid Biochem Mol Biol. 2017;173:13-22. https://doi.org/10.1016/j.jsbmb.2017.01.017

Many P, Yuktanandana P, Tanavalee A, Anomasiri W, Ngarmukos S, Tanpowpong T, et al. Vitamin D supplementation improves quality of life and physical performance in osteoarthritis patients. Nutrients. 2017;9:799. https://doi.org/10.3390/nu9080799

Heidari B, Javadian Y, Babaei M, Yousef‐Ghahari B. Restorative effect of vitamin D deficiency on knee pain and quadriceps in knee osteoarthritis. Acta Med Iran. 2015;53:466-70.

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Published

2021-07-13

How to Cite

1.
Vranić V, Zeljić K, Štefik D, Ivković N, Abazović D, Arsenijević N, Vojvodić D, Šupić G. Vitamin D receptor gene variants contribute to hip and knee osteoarthritis susceptibility. Arch Biol Sci [Internet]. 2021Jul.13 [cited 2024Nov.22];73(2):247-55. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/6442

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