Nakano Masaki, Nakamura Yukio, Urano Tomohiko, Miyazaki Akiko, Suzuki Takako, Watanabe Kazuki, Takahashi Jun, Shiraki Masataka
Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
Department of Geriatric Medicine, International University of Health and Welfare School of Medicine, 4-3 Kozunomori, Narita, Chiba 286-8686, Japan.
J Clin Endocrinol Metab. 2021 Nov 19;106(12):3428-3438. doi: 10.1210/clinem/dgab591.
Although homocysteine accumulation is a reported risk factor for several age-related disorders, little is known about its relationship with osteoarthritis (OA).
We investigated for associations of homocysteine and C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR), which is involved in homocysteine clearance, with the development and progression of spinal OA through a combined cross-sectional and longitudinal cohort study.
A total of 1306 Japanese postmenopausal outpatients participating in the Nagano Cohort Study were followed for a mean 9.7-year period. Cross-sectional multiple logistic regression for spinal OA prevalence at registration by serum homocysteine level was performed with adjustment for confounders. In addition to Kaplan-Meier analysis, multivariate Cox regression was employed to examine the independent risk of MTHFR C677T variant for spinal OA progression.
Multivariate regression analysis revealed a significant association between homocysteine and spinal OA prevalence (odds ratio 1.38; 95% CI 1.14-1.68). Kaplan-Meier curves showed a gene dosage effect of the T allele in MTHFR C677T polymorphism on the accelerated progression of spinal OA severity (P = 0.003). A statistically significant independent risk of the T allele for spinal OA advancement was validated by Cox regression analysis. Respective adjusted hazard ratios for the CT/TT and TT genotypes were 1.68 (95% CI, 1.16-2.42) and 1.67 (95% CI, 1.23-2.28).
Circulating homocysteine and C677T variant in MTHFR are associated with the prevalence rate and ensuing progression, respectively, of spinal OA. These factors may represent potential interventional targets to prevent OA development and improve clinical outcomes.
尽管有报道称同型半胱氨酸积累是几种与年龄相关疾病的风险因素，但关于其与骨关节炎（OA）的关系却知之甚少。
我们通过横断面和纵向队列研究相结合的方式，调查同型半胱氨酸以及参与同型半胱氨酸清除的亚甲基四氢叶酸还原酶（MTHFR）中的C677T多态性与脊柱OA发生和进展的关联。
共有1306名参与长野队列研究的日本绝经后门诊患者接受了平均9.7年的随访。通过血清同型半胱氨酸水平对登记时脊柱OA患病率进行横断面多因素逻辑回归分析，并对混杂因素进行调整。除了Kaplan-Meier分析外，还采用多因素Cox回归分析来检验MTHFR C677T变异对脊柱OA进展的独立风险。
多因素回归分析显示同型半胱氨酸与脊柱OA患病率之间存在显著关联（比值比1.38；95%可信区间1.14 - 1.68）。Kaplan-Meier曲线显示MTHFR C677T多态性中T等位基因对脊柱OA严重程度加速进展具有基因剂量效应（P = 0.003）。Cox回归分析验证了T等位基因对脊柱OA进展具有统计学显著的独立风险。CT/TT和TT基因型各自的调整后风险比分别为1.68（95%可信区间，1.16 - 2.42）和1.67（95%可信区间，1.23 - 2.28）。
循环中的同型半胱氨酸和MTHFR中的C677T变异分别与脊柱OA的患病率和随后的进展相关。这些因素可能是预防OA发生和改善临床结局的潜在干预靶点。
