Abstract
Osteoclast inhibitory lectin (OCIL) is a newly recognized inhibitor of mouse and human osteoclast differentiation whose cellular expression is similar to that of receptor activator of nuclear factor κB (RANKL). The main objective of the present work was to elucidate whether naturally occurring single-nucleotide polymorphisms (SNPs) in this gene could be associated with bone mass in postmenopausal women. To that end, we studied the association of bone mineral density (BMD) measured by dual-energy X-ray absorptiometry with two nonsynonymous SNPs in the OCIL gene resulting in Asn19Lys and Leu23Val substitutions in a population of 500 postmenopausal Spanish women. A weak association was detected for Asn19Lys SNP with femoral neck (FN) BMD and lumbar spine (LS) BMD in the whole population. When the population was stratified by age, however, the association was strong in older women (≥53 years). Thus, in this group of participants, women with CG/GG genotype displayed reductions of 5.6% and 6.7% in FN BMD and LS BMD adjusted by age and body mass index (BMI), respectively, compared to women with CC genotype. The Asn19Lys SNP alleles explained about 7% of BMD variance in older women but only 1.7–3.9% in the whole population in regression models including age and BMI. In conclusion, women with a lysine (GG genotype) at position 19 of the OCIL protein displayed lower BMD at femoral neck and at lumbar spine sites than women having an asparagine residue. Since the OCIL protein inhibits osteoclast differentiation, this amino acid substitution could have consequences for OCIL functionality.
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Acknowledgements
The authors are indebted to Ms. Rosa Aliaga and Ms. Elvira Calap for their excellent technical assistance. This work was supported by grants PI060154 from Fondo de Investigación Sanitaria (FIS, Madrid, Spain) and AP-024/07 from Consellería de Sanitat and 045/2007 from EVES (Generalitat Valenciana). M. A. G.-P. is a recipient of a research contract from FIS–Consellería de Sanitat (Generalitat Valenciana).
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Pineda, B., Laporta, P., Cano, A. et al. The Asn19Lys Substitution in the Osteoclast Inhibitory Lectin (OCIL) Gene is Associated with a Reduction of Bone Mineral Density in Postmenopausal Women. Calcif Tissue Int 82, 348–353 (2008). https://doi.org/10.1007/s00223-008-9135-4
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DOI: https://doi.org/10.1007/s00223-008-9135-4