Johnsen M B, Vie G Å, Winsvold B S, Bjørngaard J H, Åsvold B O, Gabrielsen M E, Pedersen L M, Hellevik A I, Langhammer A, Furnes O, Flugsrud G B, Skorpen F, Romundstad P R, Storheim K, Nordsletten L, Zwart J A
Communication and Research Unit for Musculoskeletal Disorders, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Public Health and General Practice, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Osteoarthritis Cartilage. 2017 Jun;25(6):817-823. doi: 10.1016/j.joca.2016.12.021. Epub 2017 Jan 1.
Smoking has been associated with a reduced risk of hip and knee osteoarthritis (OA) and subsequent joint replacement. The aim of the present study was to assess whether the observed association is likely to be causal.
55,745 participants of a population-based cohort were genotyped for the rs1051730 C > T single-nucleotide polymorphism (SNP), a proxy for smoking quantity among smokers. A Mendelian randomization analysis was performed using rs1051730 as an instrument to evaluate the causal role of smoking on the risk of hip or knee replacement (combined as total joint replacement (TJR)). Association between rs1051730 T alleles and TJR was estimated by hazard ratios (HRs) and 95% confidence intervals (CIs). All analyses were adjusted for age and sex.
Smoking quantity (no. of cigarettes) was inversely associated with TJR (HR 0.97, 95% CI 0.97-0.98). In the Mendelian randomization analysis, rs1051730 T alleles were associated with reduced risk of TJR among current smokers (HR 0.84, 95% CI 0.76-0.98, per T allele), however we found no evidence of association among former (HR 0.97, 95% CI 0.88-1.07) and never smokers (HR 0.97, 95% CI 0.89-1.06). Neither adjusting for body mass index (BMI), cardiovascular disease (CVD) nor accounting for the competing risk of mortality substantially changed the results.
This study suggests that smoking may be causally associated with the reduced risk of TJR. Our findings add support to the inverse association found in previous observational studies. More research is needed to further elucidate the underlying mechanisms of this causal association.
吸烟与髋部和膝部骨关节炎（OA）风险降低以及随后的关节置换有关。本研究的目的是评估观察到的这种关联是否可能是因果关系。
对一项基于人群的队列研究中的55745名参与者进行基因分型，检测rs1051730 C>T单核苷酸多态性（SNP），这是吸烟者吸烟量的一个替代指标。使用rs1051730作为工具进行孟德尔随机化分析，以评估吸烟对髋部或膝部置换（合并为全关节置换（TJR））风险的因果作用。通过风险比（HRs）和95%置信区间（CIs）估计rs1051730 T等位基因与TJR之间的关联。所有分析均根据年龄和性别进行了调整。
吸烟量（香烟数量）与TJR呈负相关（HR 0.97，95%CI 0.97 - 0.98）。在孟德尔随机化分析中，rs1051730 T等位基因与当前吸烟者中TJR风险降低有关（HR 0.84，95%CI 0.76 - 0.98，每一个T等位基因），然而我们在前吸烟者（HR 0.97，95%CI 0.88 - 1.07）和从不吸烟者（HR 0.97，95%CI 0.89 - 1.06）中未发现关联证据。调整体重指数（BMI）、心血管疾病（CVD）或考虑死亡的竞争风险均未实质性改变结果。
本研究表明吸烟可能与TJR风险降低存在因果关系。我们的发现为先前观察性研究中发现的负相关提供了支持。需要更多研究来进一步阐明这种因果关联的潜在机制。
