Suggestive linkage of the parathyroid receptor type 1 to osteoporosis

Duncan, EL, Brown, MA, Sinsheimer, J, Bell, J, Carr, AJ, Wordsworth, BP and Wass, JAH (1999) Suggestive linkage of the parathyroid receptor type 1 to osteoporosis. Journal of Bone And Mineral Research, 14 12: 1993-1999. doi:10.1359/jbmr.1999.14.12.1993

Author Duncan, EL
Brown, MA
Sinsheimer, J
Bell, J
Carr, AJ
Wordsworth, BP
Wass, JAH
Title Suggestive linkage of the parathyroid receptor type 1 to osteoporosis
Journal name Journal of Bone And Mineral Research   Check publisher's open access policy
ISSN 0884-0431
Publication date 1999-12
Sub-type Article (original research)
DOI 10.1359/jbmr.1999.14.12.1993
Volume 14
Issue 12
Start page 1993
End page 1999
Total pages 7
Place of publication Washington, D. C., U.S.A.
Publisher American Society for Bone and Mineral Research
Language eng
Subject C1
0604 Genetics
Abstract We have investigated the role of 23 candidate genes in the control of bone mineral density (BMD) by linkage studies in families of probands with osteoporosis (lumbar spine [LS] or femoral neck [FN] BMD T score < -2.5) and low BMD relative to an age- and gender-matched cohort (Z score < -2.0). One hundred and fifteen probands (35 male, 80 female) and 499 of their first- or second-degree relatives (223 males and 276 females) were recruited for the study. BMD was measured at the LS and FN using dual-energy X-ray absorptiometry and expressed as age- and gender-matched Z scores corrected for body mass index. The candidate genes studied were the androgen receptor, type I collagen A1 (COLIA1), COLIA2, COLIIA1, vitamin D receptor (VDR), colony-stimulating factor 1, calcium-sensing receptor, epidermal growth factor (EGF), estrogen receptor 1 (ESR1), fibrillin type 1, insulin-like growth factor 1, interleukin-1 alpha (IL-1α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-11 (IL-11), osteopontin, parathyroid hormone (PTH), PTH-related peptide, PTH receptor type 1 (PTHR1), transforming growth factor-beta 1, and tumor necrosis factors alpha and beta. Sixty-four microsatellites lying close to or within these genes were investigated for linkage with BMD. Using the program MapMaker/Sibs there was suggestive evidence of linkage between BMD and PTHR1 (maximum LOD score obtained [MLS] 2.7-3.5). Moderate evidence of linkage was also observed with EGF (MLS 1.8), COLIA1 (MLS 1.7), COLIIA1/VDR (MLS 1.7), ESR1 (MLS 1.4), IL-1α (MLS 1.4), IL-4 (MLS 1.2), and IL-6 (MLS 1.2). Variance components analysis using the program ACT, correcting for proband-wise ascertainment, also showed evidence of linkage (p ≤0.05) at markers close to or within the candidate genes IL- 1α, PTHR1, IL-6, and COLIIA1/VDR. Further studies will be required to confirm these findings, to refine the location of gene responsible for the observed linkage, and to screen the candidate genes targeted at these loci for mutations.
Keyword Bone-mineral-density
Hormone-related Peptide
Quantitative-trait Loci
Complex Traits
BlomstrandL Chondrodysplasia
Postmenopausal Women
Genetic Dissection
SIB Pairs
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
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Created: Tue, 07 Sep 2010, 10:02:25 EST