Relationship between COL1A1 Sp1 and COL1A2 PvuII SNPs and fractures in childhood

Background: COL1A1 and COL1A2 mutations can result in increased bone fragility but the effect of SNPs on fracture risk in childhood is poorly understood. Functional data relate the COL1A1 Sp1 T allele to reduced bone strength but its relationship with bone size and mineral content in paediatric populations is inconsistent. The conservative COL1A2 PvuII SNP was over-represented in a small prepubertal Finnish population with fractures. Aim: Our study aimed to determine whether COL1A1 Sp1 and COL1A2 PvuII SNP alleles are over-represented in a population of children in the north of England who have sustained fractures. Methods: Over 400 children aged 4–16 years presenting to hospital following trauma were divided into two approximately equal groups according to whether or not this had resulted in fracture. Each child had total body and lumbar spine DEXA scans. DNA extracted from buccal brushings was analysed for the SNPs with pyrosequencing technology. Results: There was no significant difference in frequency of the COL1A1 Sp1 TT genotype between the two groups (p=0.51; % difference 1.5% (−1.4% to 4.4%)). However the COL1A2 PvuII GG genotype was significantly lower in the fracture group compared to controls (p=0.016; % difference 8.9% (2.1% to 15.6%)). No relationship was found between genotype and bone size or mass at any site. Discussion: The COL1A2 PvuII GG genotype is less frequent in children who sustain fractures, in contrast to the Finnish data. The lack of a relationship of genotype with bone size or mass implies an effect of genotype either on bone quality or an aspect of bone architecture not captured by DEXA.