Genetic predisposition to fracture non-union: a case control study of a preliminary single nucleotide polymorphisms analysis of the BMP pathway

• Main Authors: Giannoudis Peter V, Markham Alexander F, West Robert M, Carr Ian M, Dimitriou Rozalia
• Format: Article
• Language: English
• Published: BMC 2011-02-01
• Series: BMC Musculoskeletal Disorders
• Online Access: http://www.biomedcentral.com/1471-2474/12/44

<p>Abstract</p> <p>Background</p> <p>Despite the known multi-factorial nature of atrophic fracture non-unions, a possible genetic predisposition for the development of this complication after long bone fractures remains unknown. This pilot study aimed to address this issue by performing a preliminary SNP analysis of specific genes known to regulate fracture healing.</p> <p>Methods</p> <p>A total of fifteen SNPs within four genes of the Bone Morphogenetic Protein (BMP) pathway (<it>BMP-2, BMP-7</it>, <it>NOGGIN </it>and <it>SMAD6</it>) were examined, in 109 randomly selected patients with long bone fractures as a result of motor vehicle accident, fall or direct blow. There were sixty-two patients with atrophic non-union and forty-seven patients (54 fractures) with uneventful fracture union. Overall SNPs frequencies were computed with respect to patient's age, gender, smoking habits, fracture-associated parameters and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), and tested for their association to the impaired bone healing process, using binary logistic regression (STATA 11.1; StataCorp, Texas USA).</p> <p>Results</p> <p>Statistical analysis revealed age to be an important covariate in the development of atrophic non-union (<it>p </it>= 0.01, OR 1.05 [per year]), and two specific genotypes (G/G genotype of the rs1372857 SNP, located on <it>NOGGIN </it>and T/T genotype of the rs2053423 SNP, located on <it>SMAD6</it>) to be associated with a greater risk of fracture non-union (<it>p </it>= 0.02, OR 4.56 and <it>p </it>= 0.04, OR 10.27, respectively, after adjustment for age).</p> <p>Conclusions</p> <p>This is the first clinical study to investigate the potential existence of genetic susceptibility to fracture non-union. Even though no concrete conclusions can be obtained from this pilot study, our results indicate the existence of a potential genetically predetermined impairment within the BMP signalling cascade, initiated after a fracture and when combined with other risk factors could synergistically increase the susceptibility of a patient to develop non-union. Further research is desirable in order to clarify the genetic component and its role and interaction with other risk factors in the development of atrophic long bone non-union, as simple genetic testing may contribute to the early identification of patients at risk in the future and the on-time intervention at the biologic aspects of bone healing.</p>