Genetic analysis of high bone mass cases from the BARCOS cohort of Spanish postmenopausal women.
The aims of the study were to establish the prevalence of high bone mass (HBM) in a cohort of Spanish postmenopausal women (BARCOS) and to assess the contribution of LRP5 and DKK1 mutations and of common bone mineral density (BMD) variants to a HBM phenotype. Furthermore, we describe the expression...
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2014
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oai:doaj.org-article:c695d365529f4709b72c757a857e76af2021-11-18T08:23:04ZGenetic analysis of high bone mass cases from the BARCOS cohort of Spanish postmenopausal women.1932-620310.1371/journal.pone.0094607https://doaj.org/article/c695d365529f4709b72c757a857e76af2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24736728/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The aims of the study were to establish the prevalence of high bone mass (HBM) in a cohort of Spanish postmenopausal women (BARCOS) and to assess the contribution of LRP5 and DKK1 mutations and of common bone mineral density (BMD) variants to a HBM phenotype. Furthermore, we describe the expression of several osteoblast-specific and Wnt-pathway genes in primary osteoblasts from two HBM cases. A 0.6% of individuals (10/1600) displayed Z-scores in the HBM range (sum Z-score >4). While no mutation in the relevant exons of LRP5 was detected, a rare missense change in DKK1 was found (p.Y74F), which cosegregated with the phenotype in a small pedigree. Fifty-five BMD SNPs from Estrada et al. [NatGenet 44:491-501,2012] were genotyped in the HBM cases to obtain risk scores for each individual. In this small group of samples, Z-scores were found inversely related to risk scores, suggestive of a polygenic etiology. There was a single exception, which may be explained by a rare penetrant genetic variant, counterbalancing the additive effect of the risk alleles. The expression analysis in primary osteoblasts from two HBM cases and five controls suggested that IL6R, DLX3, TWIST1 and PPARG are negatively related to Z-score. One HBM case presented with high levels of RUNX2, while the other displayed very low SOX6. In conclusion, we provide evidence of lack of LRP5 mutations and of a putative HBM-causing mutation in DKK1. Additionally, we present SNP genotyping and expression results that suggest additive effects of several genes for HBM.Patricia SarriónLeonardo MellibovskyRoser UrreiztiSergi CivitNeus ColsNatàlia García-GiraltGuy YoskovitzAlvaro ArangurenJorge MaloufSilvana Di GregorioLuís Del RíoRoberto GüerriXavier NoguésXavier NoguésAdolfo Díez-PérezDaniel GrinbergSusana BalcellsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e94607 (2014) |
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| collection |
DOAJ |
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EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Patricia Sarrión Leonardo Mellibovsky Roser Urreizti Sergi Civit Neus Cols Natàlia García-Giralt Guy Yoskovitz Alvaro Aranguren Jorge Malouf Silvana Di Gregorio Luís Del Río Roberto Güerri Xavier Nogués Xavier Nogués Adolfo Díez-Pérez Daniel Grinberg Susana Balcells Genetic analysis of high bone mass cases from the BARCOS cohort of Spanish postmenopausal women. |
| description |
The aims of the study were to establish the prevalence of high bone mass (HBM) in a cohort of Spanish postmenopausal women (BARCOS) and to assess the contribution of LRP5 and DKK1 mutations and of common bone mineral density (BMD) variants to a HBM phenotype. Furthermore, we describe the expression of several osteoblast-specific and Wnt-pathway genes in primary osteoblasts from two HBM cases. A 0.6% of individuals (10/1600) displayed Z-scores in the HBM range (sum Z-score >4). While no mutation in the relevant exons of LRP5 was detected, a rare missense change in DKK1 was found (p.Y74F), which cosegregated with the phenotype in a small pedigree. Fifty-five BMD SNPs from Estrada et al. [NatGenet 44:491-501,2012] were genotyped in the HBM cases to obtain risk scores for each individual. In this small group of samples, Z-scores were found inversely related to risk scores, suggestive of a polygenic etiology. There was a single exception, which may be explained by a rare penetrant genetic variant, counterbalancing the additive effect of the risk alleles. The expression analysis in primary osteoblasts from two HBM cases and five controls suggested that IL6R, DLX3, TWIST1 and PPARG are negatively related to Z-score. One HBM case presented with high levels of RUNX2, while the other displayed very low SOX6. In conclusion, we provide evidence of lack of LRP5 mutations and of a putative HBM-causing mutation in DKK1. Additionally, we present SNP genotyping and expression results that suggest additive effects of several genes for HBM. |
| format |
article |
| author |
Patricia Sarrión Leonardo Mellibovsky Roser Urreizti Sergi Civit Neus Cols Natàlia García-Giralt Guy Yoskovitz Alvaro Aranguren Jorge Malouf Silvana Di Gregorio Luís Del Río Roberto Güerri Xavier Nogués Xavier Nogués Adolfo Díez-Pérez Daniel Grinberg Susana Balcells |
| author_facet |
Patricia Sarrión Leonardo Mellibovsky Roser Urreizti Sergi Civit Neus Cols Natàlia García-Giralt Guy Yoskovitz Alvaro Aranguren Jorge Malouf Silvana Di Gregorio Luís Del Río Roberto Güerri Xavier Nogués Xavier Nogués Adolfo Díez-Pérez Daniel Grinberg Susana Balcells |
| author_sort |
Patricia Sarrión |
| title |
Genetic analysis of high bone mass cases from the BARCOS cohort of Spanish postmenopausal women. |
| title_short |
Genetic analysis of high bone mass cases from the BARCOS cohort of Spanish postmenopausal women. |
| title_full |
Genetic analysis of high bone mass cases from the BARCOS cohort of Spanish postmenopausal women. |
| title_fullStr |
Genetic analysis of high bone mass cases from the BARCOS cohort of Spanish postmenopausal women. |
| title_full_unstemmed |
Genetic analysis of high bone mass cases from the BARCOS cohort of Spanish postmenopausal women. |
| title_sort |
genetic analysis of high bone mass cases from the barcos cohort of spanish postmenopausal women. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/c695d365529f4709b72c757a857e76af |
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