Therapeutics and Clinical Risk Management (Sep 2021)

Associations of LRP5 and MTHFR Gene Variants with Osteoarthritis Prevalence in Elderly Women: A Japanese Cohort Survey Randomly Sampled from a Basic Resident Registry

  • Nakano M,
  • Yui H,
  • Kikugawa S,
  • Tokida R,
  • Sakai N,
  • Kondo N,
  • Endo N,
  • Haro H,
  • Shimodaira H,
  • Suzuki T,
  • Kato H,
  • Takahashi J,
  • Nakamura Y

Journal volume & issue
Vol. Volume 17
pp. 1065 – 1073

Abstract

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Masaki Nakano,1,* Haruka Yui,1,* Shingo Kikugawa,2 Ryosuke Tokida,3 Noriko Sakai,4 Naoki Kondo,5 Naoto Endo,5 Hirotaka Haro,6 Hiroki Shimodaira,1 Takako Suzuki,1,7 Hiroyuki Kato,1 Jun Takahashi,1 Yukio Nakamura1 1Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, 390-8621, Japan; 2DNA Chip Research Inc., Minato-ku, Tokyo, 105-0022, Japan; 3Rehabilitation Center, Shinshu University Hospital, Matsumoto, Nagano, 390-8621, Japan; 4Department of Orthopaedic Surgery, New Life Hospital, Obuse, Nagano, 381-0295, Japan; 5Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, 951-8510, Japan; 6Department of Orthopaedic Surgery, University of Yamanashi Graduate School of Medicine, Chuo, Yamanashi, 409-3898, Japan; 7Department of Human Nutrition, Faculty of Human Nutrition, Tokyo Kasei Gakuin University, Chiyoda-ku, Tokyo, 102-8341, Japan*These authors contributed equally to this workCorrespondence: Yukio NakamuraDepartment of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, JapanTel +81-263-37-2659Fax +81-263-35-8844Email [email protected]: Osteoarthritis (OA) is a common and degenerative joint disorder in the elderly. A greater importance of understanding the relationship between genetic factors and OA prevalence has emerged with population aging. We therefore investigated the associations of several bone disease-related genetic variants with the prevalence of OA and osteoporosis in Japanese elderly women from the Obuse study cohort, which was randomly sampled from a basic town resident registry.Methods and Results: In total, 206 female participants (mean ± standard deviation age: 69.7 ± 11.0 years) who completed OA, bone mineral density, and genotype assessments were included. The number of patients diagnosed as having knee/hip OA and osteoporosis was 59 (28.6%) and 30 (14.6%), respectively. Fisher’s exact testing revealed significant relationships between the minor T allele of LDL receptor related protein 5 (LRP5) rs3736228 and the prevalence of knee/hip OA and osteoporosis. The respective odds ratios (ORs) of the TT genotype for knee/hip OA and osteoporosis were 7.28 (95% confidence interval [CI] 2.22– 28.08) and 5.24 (95% CI 0.95– 26.98). An additional subgroup analysis for knee OA revealed that the frequency of the common C allele of methylenetetrahydrofolate reductase (MTHFR) rs1801133 had a statistically significant protective association with the prevalence of knee OA (OR 0.58, 95% CI 0.35– 0.97).Conclusion: In sum, the present study demonstrated significant associations of LRP5 rs3736228 and MTHFR rs1801133 with knee/hip OA and osteoporosis prevalences and knee OA prevalence, respectively, in Japanese elderly women. These results will help further the understanding of OA pathogenesis and related genetic risk factors.Keywords: genetic variant, LRP5, MTHFR, osteoarthritis, osteoporosis

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