Department of Nursing, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou 213000, China.
Department of Orthopedics Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, China.
Gene. 2020 Aug 15;751:144766. doi: 10.1016/j.gene.2020.144766. Epub 2020 May 12.
Approximately 10-15% of fracture patients suffer impaired healing, which is either delayed or even results in non-union. We performed a Systematic Review, aiming to examine the types and frequency of specific genetic abnormalities in patients experiencing bone fracture and to ascertain whether a genetic association exists regarding the tendency for some patients to suffer fracture non-union or postoperative non-union events. GO and KEGG analyses were used to identify the likely function of the genes involved. Furthermore, we evaluated the functional significance of single nucleotide polymorphisms using RegulomeDB and GTEx. Seven eligible studies involving 29 genes and 89 SNPs were analyzed in this review. We found that the polymorphisms in gene NOS2, NOG, BMP4, CYR61, IL1β and FGFR1 apparently predisposed patients to fracture non-union, while the polymorphisms in gene MMP13, BMP6 and FAM5C appeared to provide protection from non-union. Bioinformatics analysis suggested that these genes were enriched in inflammatory pathways, suggesting that inflammation may be a potential factor involved in fracture non-union. Three SNPs (rs17563, rs3753793 and rs2853550) had smaller RegulomeDB scores, indicating significant biological function. In conclusion, we have identified a number of genes and their polymorphisms that might contribute to a genetic susceptibility to fracture non-union. Further studies with larger cohorts will enhance our understanding of fracture non-union and may inform and direct early interventions.
大约有 10-15%的骨折患者的愈合受到影响，要么延迟，要么甚至导致骨折不愈合。我们进行了一项系统综述，旨在检查骨折患者中特定遗传异常的类型和频率，并确定是否存在一些患者容易发生骨折不愈合或术后不愈合的遗传关联。GO 和 KEGG 分析用于确定所涉及基因的可能功能。此外，我们使用 RegulomeDB 和 GTEx 评估了单核苷酸多态性的功能意义。在这项综述中，分析了七项涉及 29 个基因和 89 个 SNP 的合格研究。我们发现基因 NOS2、NOG、BMP4、CYR61、IL1β 和 FGFR1 的多态性明显使患者易患骨折不愈合，而基因 MMP13、BMP6 和 FAM5C 的多态性似乎能预防不愈合。生物信息学分析表明，这些基因富集在炎症途径中，表明炎症可能是骨折不愈合的一个潜在因素。三个 SNP(rs17563、rs3753793 和 rs2853550)的 RegulomeDB 评分较低，表明具有显著的生物学功能。总之，我们已经确定了一些可能导致骨折不愈合遗传易感性的基因及其多态性。更大样本量的进一步研究将增强我们对骨折不愈合的理解，并可能为早期干预提供信息和指导。
