Trauma and Orthopaedic Surgery, National Institute of Traumatology and Orthopaedics, Rio de Janeiro, Brazil.
J Orthop Res. 2013 Dec;31(12):1971-9. doi: 10.1002/jor.22455. Epub 2013 Aug 12.
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.
骨折愈合是一个复杂的过程，受到多种因素的影响和几千个基因的表达。这些基因的多态性可能导致愈合过程延长，并解释为什么某些患者更容易发生骨折不愈合。在 167 例长骨骨折患者（101 例愈合良好，66 例发生无菌性不愈合）中，研究了五个与骨修复发病机制相关基因（FAM5C、BMP4、FGF3、FGF10 和 FGFR1）中的 16 个 SNP。排除标准为病理性骨折、骨质疏松症、肥大性和感染性不愈合、妊娠和儿童。所有遗传标志物均采用 TaqMan 实时 PCR 进行基因分型。卡方检验用于比较各组间基因型、等位基因频率和单倍型差异。二元逻辑回归分析了多种协变量和非愈合发生率的意义。统计分析显示开放性骨折是非愈合发展的危险因素（p<0.001，OR 3.6 [1.70-7.67]）。BMP4 中的 GTAA 单倍型（p=0.01）和 FGFR1 rs13317（p=0.005）与 NU 之间存在显著关联。此外，愈合良好与 FAM5C rs1342913（p=0.04）相关。我们的工作支持 BMP4 和 FGFR1 在 NU 骨折中的作用，独立于先前描述的危险因素的存在。
