期刊
JOURNAL OF BONE AND MINERAL RESEARCH
卷 24, 期 12, 页码 1989-1997出版社
WILEY
DOI: 10.1359/JBMR.090530
关键词
filamin B; BMD; single nucleotide polymorphism; osteoporosis; fracture
资金
- Department of Twin Research and Genetic Epidemiology, KCL, UK
- Western Australian Bone and Cartilage Group
- Wellcome Trust
- Arthritis Research Campaign
- British Heart Foundation
- Chronic Disease Research Fund
- Australian National Health and Medical Research Council [294402, 343603]
- Genome Canada
- Genome Quebec
- Canada Research Chair (Tier2)
- Canadian Institutes of Health Research
- MRC [MC_U105292688] Funding Source: UKRI
- Medical Research Council [MC_U105292688] Funding Source: researchfish
- Versus Arthritis [17489] Funding Source: researchfish
Previous data from our group indicate that BMD is linked to chromosome 3p14-p21. Because the filamin B (FLNB) gene resides in this region, is the cause of skeletal dysplasias, and was identified among the top genes in our bioinformatics analysis, we hypothesized a role for FLNB in the regulation of bone structure in the general population. Using a tag single nucleotide polymorphism (SNP) approach, a family study of 767 female sibs in which the 3p14-p21 linkage with BMD was previously shown was examined. FLNB variants showing a BMD association were tested in two additional data sets, a study of 1085 UK female twins and a population study (CAIFOS) of 1315 Australian women. Genotype-expression studies were performed in 96 human osteoblast lines to examine the variants in vitro. rs7637505, rs9822918, rs2177153, and rs2001972 showed association with femoral neck (p = 0.0002-0.02) in the family-based study. The twin study provided further support for an association between rs7637505 and femoral neck and spine BMD (p = 0.02-0.03). The CAIFOS study further suggested an association between rs2177153 and rs9822918 and femoral neck BMD (p = 0.004-0.03). Prevalent fractures were increased in carriers of the A allele of rs2177153 (p = 0.009). In vitro studies showed association between rs11130605, itself in strong LD with rs7637505, and FLNB mRNA expression. These findings suggest common variants in FLNB have effects on bone structure in women. Although the location of variants having effects is not entirely consistent, variation at the 5' end of the gene may reflect effects on levels of FLNB transcription efficiency. J Bone Miner Res 2009;24:1989-1997. Published online on May 18, 2009; doi: 10.1359/JBMR.090530
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据