Zhai G, Hart D J, Kato B S, MacGregor A, Spector T D
Twin Research & Genetic Epidemiology Unit, St Thomas' Hospital, London, UK.
Osteoarthritis Cartilage. 2007 Feb;15(2):222-5. doi: 10.1016/j.joca.2006.09.004. Epub 2006 Oct 11.
Genetic influences on rates of osteoarthritis (OA) progression are unknown. Our aim was to estimate the heritability of progression of radiographic knee OA using a longitudinal twin study.
Unselected monozygotic (MZ) and dizygotic (DZ) twin pairs from the TwinsUK registry were utilized. Anteroposterior radiographs were performed on both knees at baseline and follow-up using the same protocol. Radiographic features of knee OA including osteophyte and joint space narrowing (JSN) were assessed on a four-point scale using a standard atlas. Progression of knee osteophyte and JSN was defined as the difference in the corresponding score between follow-up and baseline > or =1. Liability threshold modelling using logistic regression was utilized for heritability estimation.
A total of 114 MZ pairs and 195 DZ pairs were studied. The average follow-up time was 7.2 years. Medial progression of osteophyte and JSN was more common than lateral progression. Prevalence of progression was generally higher in the MZs than the DZs. Similarly, concordances and tetrachoric correlations for both osteophyte and JSN were higher in the MZs than the DZs although only significant for overall and medial JSN and osteophyte. The heritability estimates were 69% [95% confidence interval (CI) 42-97%] and 80% (95% CI 50-100%) for medial osteophyte and JSN, respectively. The estimates were reduced by 7-15% after adjustment for age, body mass index (BMI), and the severity of osteophyte/JSN at baseline.
Our data documented a substantial genetic influence on the progression of knee OA--as seen in the medial compartment, providing a solid basis to search for genes involved in this highly relevant clinical trait.
骨关节炎（OA）进展速率的遗传影响尚不清楚。我们的目的是通过一项纵向双胞胎研究来估计膝关节X线OA进展的遗传度。
使用来自英国双胞胎登记处未经选择的同卵（MZ）和异卵（DZ）双胞胎对。在基线和随访时，按照相同方案对双膝进行前后位X线摄影。使用标准图谱以四点量表评估膝关节OA的X线特征，包括骨赘和关节间隙变窄（JSN）。膝关节骨赘和JSN的进展定义为随访与基线时相应评分的差值>或 =1。使用逻辑回归的责任阈值模型用于遗传度估计。
共研究了114对MZ双胞胎和195对DZ双胞胎。平均随访时间为7.2年。骨赘和JSN的内侧进展比外侧进展更常见。MZ双胞胎中进展的患病率通常高于DZ双胞胎。同样，MZ双胞胎中骨赘和JSN的一致性和四分相关系数高于DZ双胞胎，尽管仅对总体和内侧JSN及骨赘有显著性。内侧骨赘和JSN的遗传度估计分别为69%[95%置信区间（CI）42 - 97%]和80%（95%CI 50 - 100%）。在对年龄、体重指数（BMI）和基线时骨赘/JSN的严重程度进行调整后，估计值降低了7 - 15%。
我们的数据记录了膝关节OA进展中存在显著的遗传影响——如在内侧间室所见，为寻找参与这一高度相关临床特征的基因提供了坚实基础。
