Research progress on the relationship between vitamin D and its receptor gene polymorphism and pain_West China Medical Journal

Authors：

WANG Yamei ¹ , LI Jie ² , LIN Jing ² ,  LIU Yingying ^1,2

1. College of Medicine and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610000, P. R. China;
2. Department of Neurology, Deyang people’s Hospital, Deyang, Sichuan 618000, P. R. China;

Corresponding author：

LIU Yingying, Email: dysrmyyliu@163.com

Keywords：

Vitamin D; pain; vitamin D receptor gene polymorphism

DOI：

10.7507/1002-0179.202503116

Video：

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Pain, as a complex physiological and pathological phenomenon, has always been a hot topic in medical research in terms of its mechanism of occurrence and influencing factors. Vitamin D, as a fat soluble vitamin, has been shown to be closely associated with pain in recent years, in addition to its classic role in regulating calcium and phosphorus metabolism. The polymorphism of the vitamin D receptor (VDR) gene can lead to changes in the structure and function of VDR, thereby affecting vitamin D levels. Meanwhile, VDR gene polymorphism can indirectly or directly participate in the occurrence and development of pain. This article aims to review the research on the relationship between vitamin D and its receptor gene polymorphism and pain, and provide reference for potential therapeutic targets and personalized intervention strategies for pain.

Citation： WANG Yamei, LI Jie, LIN Jing, LIU Yingying. Research progress on the relationship between vitamin D and its receptor gene polymorphism and pain. West China Medical Journal, 2025, 40(8): 1323-1326. doi: 10.7507/1002-0179.202503116 Copy

1.	Heidari B, Javadian Y, Babaei M, et al. Restorative effect of vitamin d deficiency on knee pain and quadriceps muscle strength in knee osteoarthritis. Acta Med Iran, 2015, 53(8): 466-470.
2.	Poisbeau P, Aouad M, Gazzo G, et al. Cholecalciferol (vitamin D3) reduces rat neuropathic pain by modulating opioid signaling. Mol Neurobiol, 2019, 56(10): 7208-7221.
3.	Banafshe HR, Khoshnoud MJ, Abed A, et al. Vitamin D supplementation attenuates the behavioral scores of neuropathic pain in rats. Nutr Neurosci, 2019, 22(10): 700-705.
4.	Guida F, Boccella S, Belardo C, et al. Altered gut microbiota and endocannabinoid system tone in vitamin D deficiency-mediated chronic pain. Brain Behav Immun, 2020, 85: 128-141.
5.	Basit A, Basit KA, Fawwad A, et al. Vitamin D for the treatment of painful diabetic neuropathy. BMJ Open Diabetes Res Care, 2016, 4(1): e000148.
6.	Chen YC, Chiang YF, Lin YJ, et al. Effect of vitamin D supplementation on primary dysmenorrhea: a systematic review and meta-analysis of randomized clinical trials. Nutrients, 2023, 15(13): 2830.
7.	Amzajerdi A, Keshavarz M, Ghorbali E, et al. The effect of vitamin D on the severity of dysmenorrhea and menstrual blood loss: a randomized clinical trial. BMC Womens Health, 2023, 23(1): 138.
8.	Rahnemaei FA, Gholamrezaei A, Afrakhteh M, et al. Vitamin D supplementation for primary dysmenorrhea: a double-blind, randomized, placebo-controlled trial. Obstet Gynecol Sci, 2021, 64(4): 353-363.
9.	Laslett LL, Quinn S, Burgess JR, 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(4): 697-703.
10.	Lee A, Lee JE. Vitamin D and the characteristics associated with risk for knee pain among Korean older adults: findings from a nationally representative survey. Geriatr Gerontol Int, 2017, 17(9): 1278-1285.
11.	Wu Z, Camargo CA Jr, Sluyter JD, et al. Association between serum 25-hydroxyvitamin D levels and self-reported chronic pain in older adults: a cross-sectional analysis from the ViDA study. J Steroid Biochem Mol Biol, 2019, 188: 17-22.
12.	Abdurahman AA, Khorrami-Nezhad L, Mirzaei K. Vitamin D (FokI) receptor gene polymorphism is associated with vitamin D deficiency and chronic musculoskeletal pain. A meta-analysis. Int J Vitam Nutr Res, 2017, 87(3/4): 219-232.
13.	Imam AA, Ibrahim HE, Farghaly MAA, et al. Vitamin D receptor gene FokI polymorphism in Egyptian children and adolescents with SLE: a case-control study. Lupus, 2017, 26(13): 1426-1434.
14.	Monticielo OA, Brenol JC, Chies JA, et al. The role of BsmI and FokI vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D in Brazilian patients with systemic lupus erythematosus. Lupus, 2012, 21(1): 43-52.
15.	Tuncel G, Temel SG, Ergoren MC. Strong association between VDR FokI (rs2228570) gene variant and serum vitamin D levels in Turkish Cypriots. Mol Biol Rep, 2019, 46(3): 3349-3355.
16.	Jia J, Tang Y, Shen C, et al. Vitamin D receptor polymorphism rs2228570 is significantly associated with risk of dyslipidemia and serum LDL levels in Chinese Han population. Lipids Health Dis, 2018, 17(1): 193.
17.	Tomei S, Singh P, Mathew R, et al. The role of polymorphisms in vitamin D-related genes in response to vitamin D supplementation. Nutrients, 2020, 12(9): 2608.
18.	Marozik P, Rudenka A, Kobets K, et al. Vitamin D status, bone mineral density, and VDR gene polymorphism in a cohort of Belarusian postmenopausal women. Nutrients, 2021, 13(3): 837.
19.	Ferraz RS, Silva CS, Cavalcante GC, et al. Variants in the VDR gene may influence 25(OH)D levels in type 1 diabetes mellitus in a Brazilian population. Nutrients, 2022, 14(5): 1010.
20.	Laczmanski L, Lwow F, Mossakowska M, et al. Association between vitamin D concentration and levels of sex hormones in an elderly Polish population with different genotypes of VDR polymorphisms (rs10735810, rs1544410, rs7975232, rs731236). Gene, 2015, 559(1): 73-76.
21.	Alhetheli G, Al-Dhubaibi MS, Bahaj SS, et al. Vitamin D receptor gene polymorphism Apai as a predisposing factor for psoriasis and its relation with serum vitamin D levels and psoriasis severity. Cureus, 2022, 14(12): e32715.
22.	Karpiński M, Galicka A, Milewski R, et al. Association between vitamin D receptor polymorphism and serum vitamin D levels in children with low-energy fractures. J Am Coll Nutr, 2017, 36(1): 64-71.
23.	Kondratyeva EI, Zakharova IN, Ilenkova NA, et al. Vitamin D status in Russian children and adolescents: contribution of genetic and exogenous factors. Front Pediatr, 2020, 8: 583206.
24.	Górczyńska-Kosiorz S, Tabor E, Niemiec P, et al. Associations between the VDR gene rs731236 (TaqI) polymorphism and bone mineral density in postmenopausal women from the RAC-OST-POL. Biomedicines, 2024, 12(4): 917.
25.	Cauci S, Migliozzi F, Trombetta CS, et al. Low back pain and FokI (rs2228570) polymorphism of vitamin D receptor in athletes. BMC Sports Sci Med Rehabil, 2017, 9: 4.
26.	Zadro J, Shirley D, Ferreira M, et al. Mapping the association between vitamin D and low back pain: a systematic review and meta-analysis of observational studies. Pain Physician, 2017, 20(7): 611-640.
27.	Zhang H, Chen L, Wang Z, et al. Association of single nucleotide polymorphism rs2228570 with lumbar disc degeneration: a case-control study and meta-analysis. J Pain Res, 2021, 14: 2001-2012.
28.	Şerifoğlu L, Yılmaz SG, Karaaslanlı A, et al. Association of TaqI (rs731236) polymorphism of vitamin D receptor gene with lumbar degenerative disc disease. World Neurosurg, 2024, 188: e419-e423.
29.	Muraki S, Dennison E, Jameson K, et al. Association of vitamin D status with knee pain and radiographic knee osteoarthritis. Osteoarthritis Cartilage, 2011, 19(11): 1301-1306.
30.	Donayeva A, Amanzholkyzy A, Nurgaliyeva R, et al. Vitamin D and vitamin D receptor polymorphism in Asian adolescents with primary dysmenorrhea. BMC Womens Health, 2023, 23(1): 414.
31.	Motaghi M, Haghjooy Javanmard S, Haghdoost F, et al. Relationship between vitamin D receptor gene polymorphisms and migraine without aura in an Iranian population. Biomed Res Int, 2013, 2013: 351942.
32.	García-Martín E, Navarro-Muñoz S, Ayuso P, et al. Vitamin D receptor and binding protein genes variants in patients with migraine. Ann Clin Transl Neurol, 2023, 10(10): 1824-1832.
33.	Papasavva M, Vikelis M, Siokas V, et al. VDR gene polymorphisms and cluster headache susceptibility: case-control study in a Southeastern European Caucasian population. J Mol Neurosci, 2022, 72(2): 382-392.
34.	Jennysdotter Olofsgård F, Ran C, Qin Y, et al. Investigating vitamin D receptor genetic markers in a cluster headache meta-analysis. Int J Mol Sci, 2023, 24(6): 5950.

1. Heidari B, Javadian Y, Babaei M, et al. Restorative effect of vitamin d deficiency on knee pain and quadriceps muscle strength in knee osteoarthritis. Acta Med Iran, 2015, 53(8): 466-470.
2. Poisbeau P, Aouad M, Gazzo G, et al. Cholecalciferol (vitamin D3) reduces rat neuropathic pain by modulating opioid signaling. Mol Neurobiol, 2019, 56(10): 7208-7221.
3. Banafshe HR, Khoshnoud MJ, Abed A, et al. Vitamin D supplementation attenuates the behavioral scores of neuropathic pain in rats. Nutr Neurosci, 2019, 22(10): 700-705.
4. Guida F, Boccella S, Belardo C, et al. Altered gut microbiota and endocannabinoid system tone in vitamin D deficiency-mediated chronic pain. Brain Behav Immun, 2020, 85: 128-141.
5. Basit A, Basit KA, Fawwad A, et al. Vitamin D for the treatment of painful diabetic neuropathy. BMJ Open Diabetes Res Care, 2016, 4(1): e000148.
6. Chen YC, Chiang YF, Lin YJ, et al. Effect of vitamin D supplementation on primary dysmenorrhea: a systematic review and meta-analysis of randomized clinical trials. Nutrients, 2023, 15(13): 2830.
7. Amzajerdi A, Keshavarz M, Ghorbali E, et al. The effect of vitamin D on the severity of dysmenorrhea and menstrual blood loss: a randomized clinical trial. BMC Womens Health, 2023, 23(1): 138.
8. Rahnemaei FA, Gholamrezaei A, Afrakhteh M, et al. Vitamin D supplementation for primary dysmenorrhea: a double-blind, randomized, placebo-controlled trial. Obstet Gynecol Sci, 2021, 64(4): 353-363.
9. Laslett LL, Quinn S, Burgess JR, 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(4): 697-703.
10. Lee A, Lee JE. Vitamin D and the characteristics associated with risk for knee pain among Korean older adults: findings from a nationally representative survey. Geriatr Gerontol Int, 2017, 17(9): 1278-1285.
11. Wu Z, Camargo CA Jr, Sluyter JD, et al. Association between serum 25-hydroxyvitamin D levels and self-reported chronic pain in older adults: a cross-sectional analysis from the ViDA study. J Steroid Biochem Mol Biol, 2019, 188: 17-22.
12. Abdurahman AA, Khorrami-Nezhad L, Mirzaei K. Vitamin D (FokI) receptor gene polymorphism is associated with vitamin D deficiency and chronic musculoskeletal pain. A meta-analysis. Int J Vitam Nutr Res, 2017, 87(3/4): 219-232.
13. Imam AA, Ibrahim HE, Farghaly MAA, et al. Vitamin D receptor gene FokI polymorphism in Egyptian children and adolescents with SLE: a case-control study. Lupus, 2017, 26(13): 1426-1434.
14. Monticielo OA, Brenol JC, Chies JA, et al. The role of BsmI and FokI vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D in Brazilian patients with systemic lupus erythematosus. Lupus, 2012, 21(1): 43-52.
15. Tuncel G, Temel SG, Ergoren MC. Strong association between VDR FokI (rs2228570) gene variant and serum vitamin D levels in Turkish Cypriots. Mol Biol Rep, 2019, 46(3): 3349-3355.
16. Jia J, Tang Y, Shen C, et al. Vitamin D receptor polymorphism rs2228570 is significantly associated with risk of dyslipidemia and serum LDL levels in Chinese Han population. Lipids Health Dis, 2018, 17(1): 193.
17. Tomei S, Singh P, Mathew R, et al. The role of polymorphisms in vitamin D-related genes in response to vitamin D supplementation. Nutrients, 2020, 12(9): 2608.
18. Marozik P, Rudenka A, Kobets K, et al. Vitamin D status, bone mineral density, and VDR gene polymorphism in a cohort of Belarusian postmenopausal women. Nutrients, 2021, 13(3): 837.
19. Ferraz RS, Silva CS, Cavalcante GC, et al. Variants in the VDR gene may influence 25(OH)D levels in type 1 diabetes mellitus in a Brazilian population. Nutrients, 2022, 14(5): 1010.
20. Laczmanski L, Lwow F, Mossakowska M, et al. Association between vitamin D concentration and levels of sex hormones in an elderly Polish population with different genotypes of VDR polymorphisms (rs10735810, rs1544410, rs7975232, rs731236). Gene, 2015, 559(1): 73-76.
21. Alhetheli G, Al-Dhubaibi MS, Bahaj SS, et al. Vitamin D receptor gene polymorphism Apai as a predisposing factor for psoriasis and its relation with serum vitamin D levels and psoriasis severity. Cureus, 2022, 14(12): e32715.
22. Karpiński M, Galicka A, Milewski R, et al. Association between vitamin D receptor polymorphism and serum vitamin D levels in children with low-energy fractures. J Am Coll Nutr, 2017, 36(1): 64-71.
23. Kondratyeva EI, Zakharova IN, Ilenkova NA, et al. Vitamin D status in Russian children and adolescents: contribution of genetic and exogenous factors. Front Pediatr, 2020, 8: 583206.
24. Górczyńska-Kosiorz S, Tabor E, Niemiec P, et al. Associations between the VDR gene rs731236 (TaqI) polymorphism and bone mineral density in postmenopausal women from the RAC-OST-POL. Biomedicines, 2024, 12(4): 917.
25. Cauci S, Migliozzi F, Trombetta CS, et al. Low back pain and FokI (rs2228570) polymorphism of vitamin D receptor in athletes. BMC Sports Sci Med Rehabil, 2017, 9: 4.
26. Zadro J, Shirley D, Ferreira M, et al. Mapping the association between vitamin D and low back pain: a systematic review and meta-analysis of observational studies. Pain Physician, 2017, 20(7): 611-640.
27. Zhang H, Chen L, Wang Z, et al. Association of single nucleotide polymorphism rs2228570 with lumbar disc degeneration: a case-control study and meta-analysis. J Pain Res, 2021, 14: 2001-2012.
28. Şerifoğlu L, Yılmaz SG, Karaaslanlı A, et al. Association of TaqI (rs731236) polymorphism of vitamin D receptor gene with lumbar degenerative disc disease. World Neurosurg, 2024, 188: e419-e423.
29. Muraki S, Dennison E, Jameson K, et al. Association of vitamin D status with knee pain and radiographic knee osteoarthritis. Osteoarthritis Cartilage, 2011, 19(11): 1301-1306.
30. Donayeva A, Amanzholkyzy A, Nurgaliyeva R, et al. Vitamin D and vitamin D receptor polymorphism in Asian adolescents with primary dysmenorrhea. BMC Womens Health, 2023, 23(1): 414.
31. Motaghi M, Haghjooy Javanmard S, Haghdoost F, et al. Relationship between vitamin D receptor gene polymorphisms and migraine without aura in an Iranian population. Biomed Res Int, 2013, 2013: 351942.
32. García-Martín E, Navarro-Muñoz S, Ayuso P, et al. Vitamin D receptor and binding protein genes variants in patients with migraine. Ann Clin Transl Neurol, 2023, 10(10): 1824-1832.
33. Papasavva M, Vikelis M, Siokas V, et al. VDR gene polymorphisms and cluster headache susceptibility: case-control study in a Southeastern European Caucasian population. J Mol Neurosci, 2022, 72(2): 382-392.
34. Jennysdotter Olofsgård F, Ran C, Qin Y, et al. Investigating vitamin D receptor genetic markers in a cluster headache meta-analysis. Int J Mol Sci, 2023, 24(6): 5950.

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Research progress on the relationship between vitamin D and its receptor gene polymorphism and pain

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