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Haplotypes of intron 4 of the estrogen receptor alpha gene and hip fractures: a replication study in Caucasians

BACKGROUND: Despite their great impact, few genetic association studies have used hip fractures as an endpoint. However, the association of two polymorphisms on intron 4 of estrogen receptor alpha (ESR1) with hip fractures was recently reported in a Chinese population. The aim of this study was to i...

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Autores principales: Velasco, Javier, Hernández, José L, Pérez-Castrillón, José L, Zarrabeitia, María T, Alonso, María A, González-Macías, Jesús, Riancho, José A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837017/
https://www.ncbi.nlm.nih.gov/pubmed/20109228
http://dx.doi.org/10.1186/1471-2350-11-16
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author Velasco, Javier
Hernández, José L
Pérez-Castrillón, José L
Zarrabeitia, María T
Alonso, María A
González-Macías, Jesús
Riancho, José A
author_facet Velasco, Javier
Hernández, José L
Pérez-Castrillón, José L
Zarrabeitia, María T
Alonso, María A
González-Macías, Jesús
Riancho, José A
author_sort Velasco, Javier
collection PubMed
description BACKGROUND: Despite their great impact, few genetic association studies have used hip fractures as an endpoint. However, the association of two polymorphisms on intron 4 of estrogen receptor alpha (ESR1) with hip fractures was recently reported in a Chinese population. The aim of this study was to investigate whether such association is also present in Caucasians. METHODS: We analyzed those two SNPs and another neighbour SNP located on the exon 4 of ESR1 in 787 patients with hip fractures and 953 controls from Spain. RESULTS: The allelic frequencies differed markedly from those reported in Asian populations. Nevertheless, haplotypes including the rs3020314 and rs1884051 loci in intron 4 showed a significant association with hip fractures (omnibus test p = 0.006 in the whole group and 0.00005 in women). In the sex-stratified analysis, the association was significant in females, but not in males. In women, the CA haplotype appeared to have a protective influence, being present in 6.5% of the controls, but only in 3% of patients with fractures (odds ratio 0.39; 95% confidence interval 0.26-0.59; estimated population preventive fraction 3.5%). The inclusion of the rs1801132 SNP of exon 4 further increased the statistical significance of the association (odds ratio 0.17; 95% CI 0.08-0.37; p = 0.00001). Each SNP appeared to contribute independently to the association. No genotype-related differences in gene expression were found in 42 femoral bone samples. CONCLUSIONS: This study confirms the association of some polymorphisms in the region of exon 4/intron 4 of ESR1 and hip fractures in women. However, there are marked differences in allele frequencies between Asian and Caucasian populations.
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spelling pubmed-28370172010-03-12 Haplotypes of intron 4 of the estrogen receptor alpha gene and hip fractures: a replication study in Caucasians Velasco, Javier Hernández, José L Pérez-Castrillón, José L Zarrabeitia, María T Alonso, María A González-Macías, Jesús Riancho, José A BMC Med Genet Research Article BACKGROUND: Despite their great impact, few genetic association studies have used hip fractures as an endpoint. However, the association of two polymorphisms on intron 4 of estrogen receptor alpha (ESR1) with hip fractures was recently reported in a Chinese population. The aim of this study was to investigate whether such association is also present in Caucasians. METHODS: We analyzed those two SNPs and another neighbour SNP located on the exon 4 of ESR1 in 787 patients with hip fractures and 953 controls from Spain. RESULTS: The allelic frequencies differed markedly from those reported in Asian populations. Nevertheless, haplotypes including the rs3020314 and rs1884051 loci in intron 4 showed a significant association with hip fractures (omnibus test p = 0.006 in the whole group and 0.00005 in women). In the sex-stratified analysis, the association was significant in females, but not in males. In women, the CA haplotype appeared to have a protective influence, being present in 6.5% of the controls, but only in 3% of patients with fractures (odds ratio 0.39; 95% confidence interval 0.26-0.59; estimated population preventive fraction 3.5%). The inclusion of the rs1801132 SNP of exon 4 further increased the statistical significance of the association (odds ratio 0.17; 95% CI 0.08-0.37; p = 0.00001). Each SNP appeared to contribute independently to the association. No genotype-related differences in gene expression were found in 42 femoral bone samples. CONCLUSIONS: This study confirms the association of some polymorphisms in the region of exon 4/intron 4 of ESR1 and hip fractures in women. However, there are marked differences in allele frequencies between Asian and Caucasian populations. BioMed Central 2010-01-28 /pmc/articles/PMC2837017/ /pubmed/20109228 http://dx.doi.org/10.1186/1471-2350-11-16 Text en Copyright ©2010 Velasco et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Velasco, Javier
Hernández, José L
Pérez-Castrillón, José L
Zarrabeitia, María T
Alonso, María A
González-Macías, Jesús
Riancho, José A
Haplotypes of intron 4 of the estrogen receptor alpha gene and hip fractures: a replication study in Caucasians
title Haplotypes of intron 4 of the estrogen receptor alpha gene and hip fractures: a replication study in Caucasians
title_full Haplotypes of intron 4 of the estrogen receptor alpha gene and hip fractures: a replication study in Caucasians
title_fullStr Haplotypes of intron 4 of the estrogen receptor alpha gene and hip fractures: a replication study in Caucasians
title_full_unstemmed Haplotypes of intron 4 of the estrogen receptor alpha gene and hip fractures: a replication study in Caucasians
title_short Haplotypes of intron 4 of the estrogen receptor alpha gene and hip fractures: a replication study in Caucasians
title_sort haplotypes of intron 4 of the estrogen receptor alpha gene and hip fractures: a replication study in caucasians
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837017/
https://www.ncbi.nlm.nih.gov/pubmed/20109228
http://dx.doi.org/10.1186/1471-2350-11-16
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