Association Between Serum 25-Hydroxyvitamin D Concentrations, CDX2 Polymorphism in Promoter Region of Vitamin D Receptor Gene, and Chronic Pain in Rural Japanese Residents

Keita Suzuki; Hiromasa Tsujiguchi; Akinori Hara; Oanh Kim Pham; Sakae Miyagi; Thao Thi Thu Nguyen; Haruki Nakamura; Fumihiko Suzuki; Tomoko Kasahara; Yukari Shimizu; Yohei Yamada; Yasuhiro Kambayashi; Hirohito Tsuboi; Takehiro Sato; Takayuki Kannon; Kazuyoshi Hosomichi; Atsushi Tajima; Toshinari Takamura; Hiroyuki Nakamura

doi:10.2147/JPR.S356630

Association Between Serum 25-Hydroxyvitamin D Concentrations, CDX2 Polymorphism in Promoter Region of Vitamin D Receptor Gene, and Chronic Pain in Rural Japanese Residents

J Pain Res. 2022 May 23:15:1475-1485. doi: 10.2147/JPR.S356630. eCollection 2022.

Authors

Keita Suzuki¹, Hiromasa Tsujiguchi^{1

2

3}, Akinori Hara^{1

2

3}, Oanh Kim Pham¹, Sakae Miyagi^{3

4}, Thao Thi Thu Nguyen⁵, Haruki Nakamura¹, Fumihiko Suzuki^{2

6}, Tomoko Kasahara², Yukari Shimizu⁷, Yohei Yamada², Yasuhiro Kambayashi⁸, Hirohito Tsuboi⁹, Takehiro Sato^{3

10}, Takayuki Kannon^{3

10}, Kazuyoshi Hosomichi^{3

10}, Atsushi Tajima^{3

10}, Toshinari Takamura¹¹, Hiroyuki Nakamura^{1

2

3}

Affiliations

¹ Department of Hygiene and Public Health, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
² Department of Public Health, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
³ Kanazawa University Advanced Preventive Medical Sciences Research Center, Kanazawa, Ishikawa, Japan.
⁴ Innovative Clinical Research Center, Kanazawa University, Kanazawa, Ishikawa, Japan.
⁵ Department of Epidemiology, Faculty of Public Health, Haiphong University of Medicine and Pharmacy, Hai Phong, Vietnam.
⁶ Community Medicine Support Dentistry, Ohu University Hospital, Koriyama, Fukushima, Japan.
⁷ Department of Nursing, Faculty of Health Sciences, Komatsu University, Komatsu, Ishikawa, Japan.
⁸ Department of Public Health, Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, Japan.
⁹ Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
¹⁰ Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
¹¹ Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.

Abstract

Background: Previous studies examined the association between chronic pain (CP) and serum 25-hydroxyvitamin D (25(OH)D) concentrations; however, the findings obtained were inconsistent. Single nucleotide polymorphisms (SNP) associated with the transcriptional activity of the vitamin D receptor (VDR) gene may influence the association of 25(OH)D levels with CP. We aimed to clarify the association between CP, serum 25(OH)D concentration, and SNPs.

Methods: In the Shika study, we performed a cross-sectional analysis of 551 participants older than 40 years who were asked whether they had been having persistent pain lasting for at least 3 months in any part of the body on a self-administered questionnaire. Serum 25(OH)D concentrations were assessed as a biomarker of the vitamin D status using a radioimmunoassay. rs731236, rs7975232, rs1544410, rs2228570, and rs11568820 were identified using peripheral blood samples, and participants were assigned to those with or without the minor allele for each SNP.

Results: The prevalence of CP was 37.2%. We observed a tendency for lower 25(OH)D levels in participants with CP than in those without CP in the hetero/minor group of rs11568820, which is a polymorphism within the CDX2-binding site in the 1e promoter region of the VDR gene. Furthermore, a logistic regression analysis revealed that lower serum 25(OH)D concentrations were significantly associated with CP in the hetero/minor group, but not in the major group.

Conclusion: These results suggest that sufficient serum 25(OH)D concentration reduces the risk of CP in individuals with the minor allele of the CDX2 polymorphism.

Keywords: 25-hydroxyvitamin D; chronic pain; epidemiology; polymorphism; promoter; vitamin D receptor gene.

Grants and funding

The present study was funded by a Grant-in-Aid for Scientific Research (B) (number: JP19H03882) and a Grant-in-Aid for Research Activity Start-up (number: JP21K21251) by the Japan Society for the Promotion of Science.