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J Orthop Res. 2014 Jan;32(1):1-7. doi: 10.1002/jor.22473. Epub 2013 Aug 27.

Meta-analysis of hypercoagulability genetic polymorphisms in Perthes disease.

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Department of Orthopaedics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewee, Bangkok, 10400, Thailand.


Perthes disease is an osteonecrosis of the femoral epiphysis with unclear etiology. This study aimed to systematically review the association between genetic determinants of hypercoagulability (Factor V Leiden, prothrombin II, and methylenetetrahydrofolate reductase; MTHFR) and Perthes disease. PubMed and Scopus searched from inception to January 2012, data extraction and quality assessment were performed. The odds ratio (OR) for the allele effect was pooled, and heterogeneity and publication bias were assessed. Twelve case-control studies met inclusion criteria and had sufficient data for extraction. There were 824 cases and 2,033 controls with a mean age range of 6.1-14.7 years. The prevalence of the minor allele in controls was 0.015 (95% confidence interval (CI): 0.008, 0.023), 0.012 (95% CI: 0.008, 0.017), and 0.105 (95% CI: 0.044, 0.167) for factor V Leiden, prothrombin II, and MTHFR, respectively. The factor V Leiden allele increased the risk of Perthes with a pooled OR of 3.10 (95% CI: 1.68, 5.72), while prothrombin II and MTHFR had non-significantly pooled OR 1.48 (95% CI: 0.71, 3.08), and 0.97 (95% CI: 0.72, 1.30), respectively. The factor V Leiden mutation is significantly related to Perthes disease, and its screening in at-risk children might be useful in the future.


Factor V Leiden; Legg-Calve-Perthes disease; etiology; genes; thrombophilia

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