Polymorphisms in BMP4 and FGFR1 genes are associated with fracture non‐union |
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Authors: | João Matheus Guimarães Isabel Cristina do Val Guimarães Maria Eugenia Leite Duarte Thays Vieira Verônica Fernandes Vianna Marco Bernardo Cury Fernandes Alexandre Rezende Vieira Priscila Ladeira Casado |
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Affiliation: | 1. Trauma and Orthopaedic Surgery, National Institute of Traumatology and Orthopaedics, , Rio de Janeiro, Brazil;2. Professor, Department of Surgery, School of Medicine, Fluminense Federal University, , Rio de Janeiro, Brazil;3. Research Division of the National Institute of Traumatology and Orthopaedics, Federal University of Rio de Janeiro, , Rio de Janeiro, Brazil;4. Professor, Institute of Health Sciences, Federal University of Rio de Janeiro, , Rio de Janeiro, Brazil;5. Biology Student, School of Biology, Fluminense Federal University, , Rio de Janeiro, Brazil;6. Orthopaedic Surgery, National Institute of Traumatology and Orthopaedics, , Rio de Janeiro, Brazil;7. Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, , Pittsburgh, Pennsylvania;8. Department of Pediatric Dentistry, and Center for Craniofacial and Dental Genetics, Department of Human Genetics, University of Pittsburgh, , Pittsburgh, Pennsylvania;9. Research Division of the National Institue of Traumatology and Orthopaedics, , Rio de Janeiro, Rio de Janeiro, 20940‐070 Brazil |
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Abstract: | Fracture healing is a complex process influenced by a multitude of factors and expression of several thousand genes. Polymorphisms in these genes can lead to an extended healing process and explain why certain patients are more susceptible to develop non‐union. A total of 16 SNPs within five genes involved in bone repair pathogenesis (FAM5C, BMP4, FGF3, FGF10, and FGFR1) were investigated in 167 patients with long bone fractures, 101 with uneventful healing, and 66 presenting aseptic non‐unions. Exclusion criteria were patients presenting pathological fractures, osteoporosis, hypertrophic and infected non‐unions, pregnancy, and children. All genetic markers were genotyped using TaqMan real‐time PCR. Chi‐square test was used to compare genotypes, allele frequencies, and haplotype differences between groups. Binary logistic regression analyzed the significance of many covariates and the incidence of non‐union. Statistical analysis revealed open fracture to be a risk factor for non‐union development (p < 0.001, OR 3.6 [1.70–7.67]). A significant association of haplotype GTAA in BMP4 (p = 0.01) and FGFR1 rs13317 (p = 0.005) with NU could be observed. Also, uneventful healing showed association with FAM5C rs1342913 (p = 0.04). Our work supported the role of BMP4 and FGFR1 in NU fracture independently of the presence of previously described risk factors. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1971–1979, 2013 |
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Keywords: | bone healing fracture repair non‐union polymorphism haplotype |
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