@article{10902/6248,
year = {2011},
month = {1},
url = {http://hdl.handle.net/10902/6248},
abstract = {Objectives. Genes explaining the susceptibility to osteoporosis have not been fully elucidated. Our objective was to explore the association of polymorphisms capturing common variations of the lipoprotein receptor related protein (LRP) 5 and 6 genes, encoding two Wnt receptors, with femoral neck bone mineral density (BMD) and osteoporotic fractures of the spine and the hip. Design. Cross-sectional, case-control and replication genetic association study. Methods. Thirty nine tagging and functional single nucleotide polymorphisms (SNP) were analyzed in a group of 1043 postmenopausal women and 394 women with hip fractures. The results were replicated in a different group of 342 women. Results. Three SNPs of the LRP6 gene were associated with BMD (nominal uncorrected pvalues< 0.05) in the discovery cohort. One showed a significant association after multiple test correction; two of them were also associated in the replication cohort, with a combined standardized mean difference of 0.51 (p=0.009) and 0.65 (p<0.0001) across rs11054704 and rs2302685 genotypes. In the discovery cohort, several LRP5 SNPs were associated with vertebral fractures (odds ratio 0.67; p=0.01), with hip fractures (unadjusted odds ratios between 0.59 and 1.21, p=0.005-0.033, but not significant after multiple test- or age-adjustment), and with height and the projected femoral neck area, but not with BMD. Transcripts of LRP5 and LRP6 were similarly abundant in bone samples. Conclusions. In this study we found common polymorphisms of LRP5 associated with osteoporotic fractures, and polymorphisms of the LRP6 gene associated with BMD, thus suggesting them as likely candidates to contribute explaining the hereditary influence on osteoporosis.},
publisher = {BioScientifica},
publisher = {European Journal of Endocrinology. 2011 Jan;164(1):123-31},
title = {Wnt receptors, bone mass, and fractures: gene-wide association analysis of LRP5 and LRP6 polymorphisms with replication},
author = {Riancho Moral, José Antonio and Olmos Martínez, José Manuel and Pineda Merlo, Begoña and García Ibarbia, María del Carmen and Pérez Núñez, María Isabel and Nan, Daniel and Velasco Montes, Javier and Cano Sánchez, Antonio and García Pérez, Miguel A. and Zarrabeitia Cimiano, María Teresa and González Macías, Jesús},
}