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SNPs provide clues about which genes may influence fracture healing
DOI:10.1038/bonekey.2015.62
This population-based, case-controlled study set out to discover whether patients with impaired or delayed fracture healing have single nucleotide polymorphisms (SNPs) within key genes that regulate bone formation.
Sixty-two adult patients were selected from a database of long-bone fracture cases that required surgical treatment; in 29 the fractures had healed normally but 33 had experienced atrophic nonunion. Both groups of patients provided samples of cheek cells to enable SNP genotyping in 30 candidate genes.
The authors report that three SNPs were significantly associated with delayed fracture healing. Of these, the most significant was within the gene encoding interleukin 1 beta, which is a known stimulator of osteoblastogenesis. The others both occurred in the gene that codes for nitric oxide synthase (NOS), a gene known to be expressed in the early stages of fracture healing.
Two further SNPs were significantly associated with improved fracture healing, so had a protective effect; one was within the gene coding for matrix metallopeptidase 13 and while the other was within the gene for bone morphogenetic protein 6. MMP13 is produced by osteoblasts and chondrocytes in the callus that forms during fracture healing; BMP6 is known to influence mesenchymal stem cells to differentiate into osteoblasts in vitro.
Editor’s comment: Discovery of the novel SNPs and genes that influence fracture healing will require a genome-wide analysis involving much larger samples of homogenous cases and matched controls.
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