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Summary Objectives: The RANK/RANKL/OPG system is involved in the determination of bone mineral density (BMD) and bone microarchitecture. Our study seeks to evaluate if there are SNPs in the 3'UTR region of the RANK gene associated with osteoporotic phenotypes. Material and methods: Seven genetic variants in 1,098 women from the BARCOS cohort were genotyped, and their association with BMD and osteoporotic fractures evaluated. An interaction with SNP rs9594738 in the RANKL gene which was previously associated with BMD was tested. Results: None of the SNPs were associated significantly with BMD. SNP rs78326403 was associated with wrist/forearm fractures (Log-additive model odds ratio (OR)=3.12 [IC 95%: 1.69 ; 5.75]; p=7.16x10 -4 ), while SNP rs884205 was associated with fractures of the spinal column (OR=4.05 Recessive; [95% CI: 1.59 ; 10.35]; p=8.24x10 -3 ). Lastly, an interaction was detected between SNP rs9594738 from RANKL and rs78326403 from RANK on the presence of fracture (p=0.039). The analysis of the effects of combined genotypes rs9594738 and rs78326403 pointed to an increase in the prevalence of fractures in subjects with a greater number of unfavourable alleles, the ORs being 2.76 [95% CI: 1.30 ; 5.81]; p=0.007) and 5.14 [95% CI: 1.37 ; 15.67]; p=0.007) for 2 and ≥3 unfavourable alleles respectively, in comparison with none/1. Conclusions: Two SNPs in 3'UTR from the RANK gene predispose to site-dependent osteoporotic fracture. An interaction with SNP rs9594738 from RANKL suggests an additive effect of BMD and bone strength.

SNPs en el 3'UTR de gen RANK determinan la fractura osteoporótica sitio-dependiente