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

BMC Medical Genetics

Research Article

José L Pérez-Castrillón¹  José L Hernández²  Jesús González-Macías²  José A Riancho²  Javier Velasco²  María A Alonso³  María T Zarrabeitia⁴ 

[1] Department of Internal Medicine, Hospital U. Río Hortega, University of Valladolid, RETICEF, Valladolid, Spain;Department of Internal Medicine, Hospital U.M. Valdecilla, University of Cantabria, RETICEF, Santander, Spain;Department of Traumatology, Hospital U.M. Valdecilla, University of Cantabria, Santander, Spain;Unit of Legal Medicine, University of Cantabria, Santander, Spain;

关键词: Bone Mineral Density;    Vertebral Fracture;    Fracture Risk;    Fracture Group;    Allelic Frequency Distribution;   

DOI  :  10.1186/1471-2350-11-16

 received in 2009-09-08, accepted in 2010-01-28,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundDespite 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.MethodsWe 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.ResultsThe 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.ConclusionsThis 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.

【 授权许可】

Unknown   
© Velasco et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. 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.