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,1 Hiromasa Tsujiguchi,1– 3 Akinori Hara,1– 3 Oanh Kim Pham,1 Sakae Miyagi,3,4 Thao Thi Thu Nguyen,5 Haruki Nakamura,1 Fumihiko Suzuki,2,6 Tomoko Kasahara,2 Yukari Shimizu,7 Yohei Yamada,2 Yasuhiro Kambayashi,8 Hirohito Tsuboi,9 Takehiro Sato,3,10 Takayuki Kannon,3,10 Kazuyoshi Hosomichi,3,10 Atsushi Tajima,3,10 Toshinari Takamura,11 Hiroyuki Nakamura1– 3 1Department of Hygiene and Public Health, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; 2Department of Public Health, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; 3Kanazawa University Advanced Preventive Medical Sciences Research Center, Kanazawa, Ishikawa, Japan; 4Innovative Clinical Research Center, Kanazawa University, Kanazawa, Ishikawa, Japan; 5Department of Epidemiology, Faculty of Public Health, Haiphong University of Medicine and Pharmacy, Hai Phong, Vietnam; 6Community Medicine Support Dentistry, Ohu University Hospital, Koriyama, Fukushima, Japan; 7Department of Nursing, Faculty of Health Sciences, Komatsu University, Komatsu, Ishikawa, Japan; 8Department of Public Health, Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, Japan; 9Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; 10Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; 11Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, JapanCorrespondence: Keita Suzuki, Department of Hygiene and Public Health, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1, Takara-machi, Kanazawa, Ishikawa, 920-8640, Japan, Tel +81 76 265 2218, Fax +81 76 234 4233, Email ksuzuk@staff.kanazawa-u.ac.jpBackground: 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: chronic pain, 25-hydroxyvitamin D, vitamin D receptor gene, promoter, polymorphism, epidemiology