Table 1.

Summary of human studies that have investigated genes related to nonunion.

Author and date	Groups	Exclusion criteria	Methods	Genes related to nonunion
Dimitriou et al., 2011	62 patients with atrophic nonunion 47 patients with normal fracture healing	None	SNP analysis	Risk factors of nonunion: G/G genotype of the rs1372857 SNP located within NOGGIN, T/T genotype of the rs2053423 SNP located within SMAD6
Zeckey et al., 2011	50 patients with femoral and tibial nonunion 44 patients with normal fracture healing	Smoking, diabetes, bilateral fractures, use of corticoids and septic nonunion	SNP analysis	Risk factors of nonunion: A PDGF haplotype (rs1800814, rs62433334, rs13309625; CCG)
Grzegorz Szczęsny et al., 2011	151 patients with nonunion 144 patients with normal fracture healing	Open fractures, massive contusion of soft tissues covering the fracture gap, trophic lesions of soft tissues, chronic inflammatory foci and diseases requiring medication with immunosuppressive drugs.	Mutation frequency found using gene analysis	Risk factors of nonunion: T/T and C/T genotype of TGF-β gene codon 10, mutated TLR4 gene W/1
Sathyendra et al., 2014	33 patients with atrophic nonunion 29 patients with normal fracture healing	None	SNP analysis	Risk factors of nonunion: (OR>1): C/T or T/T genotype at SNP rs2853550 within the IL1B gene, the C/T or T/T genotype at rs2297514 and the A/G or G/G genotype at rs2248814 within the NOS2 gene Protective factors (OR<1): G/G at rs3819089 within the MMP13 gene, G/G at rs270393 within the BMP6 gene
Sabir Ali et al., 2015	250 patients with nonunion 250 patients with normal fracture healing	Children and patients with a known systemic inflammatory disease, osteoporosis and other metabolic bone diseases, pathological fractures and subsequent nonunion and hypertrophic and infected nonunion	SNP analysis	Risk factors of nonunion: T/G genotype at SNP rs3753793 within the CYR61 gene
João Matheus Guimarães et al., 2013	66 patients with nonunion 101 patients with normal fracture healing	Patients presenting with pathological fractures, osteoporosis, other bone diseases that could interfere with calcium or phosphorus metabolism, hypertrophic and infected nonunion, pregnancy, and aged younger than 18 years	SNP analysis	Risk factors of nonunion: A BMP4 haplotype (rs2761884, rs17563, rs2071047, rs762642; GTAA); C allele at rs13317 within the FGFR1 gene Protective factors: G/T and G/G genotype at rs1342913 within the FAM5C gene
G. Zimmermann et al., 2012	8 patients with nonunion 7 patients with normal fracture healing	Renal insufficiency, liver disease, malignant tumours, collagenosis, inflammatory bowel disease, haematological diseases, long-term treatment with steroidal or nonsteroidal antiphlogistic drugs or other immunosuppressive agents, thromboprophylactic agents, fluoroquinolones and tetracyclines, hormone substitution and smoking	cDNA array analysis	Eight genes are overexpressed in the nonunion tissue: CDO1, COMP, FMOD, FN1, CLU, TCS22, ACTA2 and PDE4DIP

SNP = single nucleotide polymorphism.