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Conference Paper: Association of a single nucleotide polymorphism in low-density lipoprotein receptor-related protein 5 (LRP5) gene promoter region with peak bone mineral density: A case-control study

TitleAssociation of a single nucleotide polymorphism in low-density lipoprotein receptor-related protein 5 (LRP5) gene promoter region with peak bone mineral density: A case-control study
Authors
Issue Date2005
PublisherJohn Wiley & Sons, Inc.
Citation
The 27th Annual Meeting of the American Society for Bone and Mineral Research, Nashville, TN, 23-27 September 2005. In Journal of Bone and Mineral Research, 2005, v. 20 n. S1, Abstract no. SU191 How to Cite?
AbstractLow-density lipoprotein receptor-related protein 5 (LRP5) is important for osteoblast differentiation and mutations of the gene are associated with both low and high bone mass syndromes. To determine the importance of LRP5 in determining peak bone mass acquisition in the general population, we performed a population-based case control study. 187 pairs of sex and age matched case-control pairs (mean 36.4, range 20--44 years) of southern Chinese in ethnicity were evaluated. Cases were subjects having a BMD Z score at either the hip or spine ≤-1.28, which is equivalent to the lowest 10th percentile of the population, and controls were subjects having a BMD Z score Z ≥+1. Mutations and single nucleotide polymorphisms (SNPs) were determined in 30 case-control pairs of subjects by sequencing 3000 bp in the promoter region, all the coding exons and 100bp upstream and downstream of the adjacent intronic regions. Using this gene-based approach, 8 SNPs with a minor allele frequency >5% were studied. BMD were adjusted for age, sex and body weight and height. The results showed that subjects bearing a variant T allele (TT and TC) at the C-864T polymorphism (rs682429) in the promoter region was significantly associated with lower BMD at the lumbar spine (p= 0.006), trochanter (p= 0.016) and total hip (p= 0.014). When the two sex were analyzed separately, this polymorphic site was associated with a reduction in BMD in men at all sites measured (lumbar spine -15.6%, p= 0.01, femoral neck -15.9%, p=0.04; trochanter -15.9%, p=0.04 and total hip -15.1%, p=0.03), and in women at the lumbar spine (-3.7%, p=0.03). Haplotype TATGCCAC was associated with lower BMD in female at the lumbar spine (p=0.01), femoral neck (p=0.003), trochanter (p=0.002) and total hip (p=0.001). The C allele was associated with a 2.9 folds low risk of low BMD (Z score<-1.28) in whole population, and 2.6 folds low risk of low BMD in female. The C-864T polymorphic site is 2 bases adjacent to a consensus recognition site for the Elk-1 binding element. In conclusion, C-864T polymorphism of LRP5 is associated with low BMD in both young men and women, and may be a useful marker for predicting low peak bone mass.
Persistent Identifierhttp://hdl.handle.net/10722/102288
ISSN

 

DC FieldValueLanguage
dc.contributor.authorCheung, CLen_HK
dc.contributor.authorNg, WWen_HK
dc.contributor.authorLai, MHen_HK
dc.contributor.authorChan, VNYen_HK
dc.contributor.authorKung, AWCen_HK
dc.date.accessioned2010-09-25T20:24:36Z-
dc.date.available2010-09-25T20:24:36Z-
dc.date.issued2005en_HK
dc.identifier.citationThe 27th Annual Meeting of the American Society for Bone and Mineral Research, Nashville, TN, 23-27 September 2005. In Journal of Bone and Mineral Research, 2005, v. 20 n. S1, Abstract no. SU191-
dc.identifier.issn1523-4681-
dc.identifier.urihttp://hdl.handle.net/10722/102288-
dc.description.abstractLow-density lipoprotein receptor-related protein 5 (LRP5) is important for osteoblast differentiation and mutations of the gene are associated with both low and high bone mass syndromes. To determine the importance of LRP5 in determining peak bone mass acquisition in the general population, we performed a population-based case control study. 187 pairs of sex and age matched case-control pairs (mean 36.4, range 20--44 years) of southern Chinese in ethnicity were evaluated. Cases were subjects having a BMD Z score at either the hip or spine ≤-1.28, which is equivalent to the lowest 10th percentile of the population, and controls were subjects having a BMD Z score Z ≥+1. Mutations and single nucleotide polymorphisms (SNPs) were determined in 30 case-control pairs of subjects by sequencing 3000 bp in the promoter region, all the coding exons and 100bp upstream and downstream of the adjacent intronic regions. Using this gene-based approach, 8 SNPs with a minor allele frequency >5% were studied. BMD were adjusted for age, sex and body weight and height. The results showed that subjects bearing a variant T allele (TT and TC) at the C-864T polymorphism (rs682429) in the promoter region was significantly associated with lower BMD at the lumbar spine (p= 0.006), trochanter (p= 0.016) and total hip (p= 0.014). When the two sex were analyzed separately, this polymorphic site was associated with a reduction in BMD in men at all sites measured (lumbar spine -15.6%, p= 0.01, femoral neck -15.9%, p=0.04; trochanter -15.9%, p=0.04 and total hip -15.1%, p=0.03), and in women at the lumbar spine (-3.7%, p=0.03). Haplotype TATGCCAC was associated with lower BMD in female at the lumbar spine (p=0.01), femoral neck (p=0.003), trochanter (p=0.002) and total hip (p=0.001). The C allele was associated with a 2.9 folds low risk of low BMD (Z score<-1.28) in whole population, and 2.6 folds low risk of low BMD in female. The C-864T polymorphic site is 2 bases adjacent to a consensus recognition site for the Elk-1 binding element. In conclusion, C-864T polymorphism of LRP5 is associated with low BMD in both young men and women, and may be a useful marker for predicting low peak bone mass.-
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc.-
dc.relation.ispartofJournal of Bone and Mineral Researchen_HK
dc.titleAssociation of a single nucleotide polymorphism in low-density lipoprotein receptor-related protein 5 (LRP5) gene promoter region with peak bone mineral density: A case-control studyen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailChan, VNY: vnychana@hkucc.hku.hken_HK
dc.identifier.emailKung, AWC: awckung@hku.hken_HK
dc.identifier.authorityChan, VNY=rp00320en_HK
dc.identifier.authorityKung, AWC=rp00368en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/jbmr.5650201305-
dc.identifier.hkuros112613en_HK

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