Suggestive linkage of the parathyroid receptor type 1 to osteoporosis

Duncan, Emma L., Brown, Matthew A., Sinsheimer, Janet, Bell, John, Carr, Andrew J., Wordsworth, B. Paul, & Wass, John A.H. (1999) Suggestive linkage of the parathyroid receptor type 1 to osteoporosis. Journal of Bone and Mineral Research, 14(12), pp. 1993-1999.

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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.

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ID Code: 89557
Item Type: Journal Article
Refereed: Yes
Keywords: androgen receptor, calcium sensing receptor, collagen type 1, colony stimulating factor 1, epidermal growth factor, estrogen receptor, fibrillin, interleukin 11, interleukin 1alpha, interleukin 4, interleukin 6, lymphotoxin, osteopontin, parathyroid hormone, parathyroid hormone receptor, parathyroid hormone related protein, somatomedin C, transforming growth factor beta1, tumor necrosis factor alpha, vitamin D receptor, adolescent, adult, aged, article, bone density, controlled study, dual energy X ray absorptiometry, family study, female, femur neck, genetic linkage, human, lumbar spine, major clinical study, male, osteoporosis, Humans, Linkage (Genetics), Lod Score, Microsatellite Repeats, Middle Aged, Polymorphism, Genetic, Receptors, Parathyroid Hormone, Spine
DOI: 10.1359/jbmr.1999.14.12.1993
ISSN: 0884-0431
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 1999 ASBMR
Deposited On: 27 Oct 2015 03:18
Last Modified: 20 Mar 2016 23:33

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