To investigate the association of polymorphisms within candidate genes which we hypothesized may contribute to
stress fracture predisposition, a case-control, cross- sectional study design was employed. Genotyping 268 Single Nucleotide Polymorphisms- SNPs within 17 genes in 385 Israeli young male and female recruits (182 with and 203 without
stress fractures). Twenty-five polymorphisms within 9 genes (NR3C1, ANKH, VDR, ROR2, CALCR,
IL6,
COL1A2,
CBG, and LRP4) showed statistically significant differences (p < 0.05) in the distribution between
stress fracture cases and non
stress fracture controls. Seventeen genetic variants were associated with an increased
stress fracture risk, and eight variants with a decreased
stress fracture risk. None of the SNP associations remained significant after correcting for multiple comparisons (false discovery rate- FDR). Our findings suggest that genes may be involved in
stress fracture pathogenesis. Specifically, the CALCR and the VDR genes are intriguing candidates. The putative involvement of these genes in
stress fracture predisposition requires analysis of more cases and controls and sequencing the relevant genomic regions, in order to define the specific gene mutations. Key pointsUnderstanding the possible contribution of genetic variants to
stress fracture pathogenesis.There is a paucity of data on the involvement of polymorphisms in specific genes in active military personnel/athletes which may contribute to
stress fractures development.The results from the current study should facilitate a more comprehensive look at the genetic component of
stress fractures.