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Absence of linkage for bone mineral density to chromosome 12q12-14 in the region of the vitamin D receptor gene

Item Type:Article
Title:Absence of linkage for bone mineral density to chromosome 12q12-14 in the region of the vitamin D receptor gene
Creators Name:Zee, R.Y.L. and Myers, R.H. and Hannan, M.T. and Wilson, P.W.F. and Ordovas, J.M. and Schaefer, E.J. and Lindpaintner, K. and Kiel, D.P.
Abstract:Polymorphisms in the region of the gene for the vitamin D receptor (VDR) (chromosome 12q12-14) have been associated with differences in bone mineral density (BMD) in some studies but not in others. Because linkage analysis assesses allele sharing identical-by-descent among relatives instead of the association of a particular allele of an anonymous marker, we have performed a linkage study for bone BMD using microsatellite markers flanking the VDR locus. The present study explores whether or not relatives who share the chromosomal region containing the VDR gene have more similar bone density. Participants in the Framingham Osteoporosis Study (aged 37-89 years) who had undergone BMD testing were used to test for concordance of genotype with phenotype in the hip (femoral neck, Ward's area, trochanter) and lumbar spine (L2-L4) with adjustment for covariates. Multipoint quantitative trait linkage analysis using variance components methods was conducted with microsatellite markers flanking the VDR locus (GATA91H06, GATA5A09, GGAT2G06) in 332 extended families containing 1062 individuals with both bone density measures and marker data. In addition, quantitative trait sib-pair linkage analysis, with a marker (AFM345xf1) in close proximity to the VDR locus, was performed in a second sample of 169 sibships (n = 413), comprising 284 full-sib pairs. Neither analysis revealed evidence for linkage of this region to femoral neck, Ward's area, lumbar spine, and trochanter in age or sex BMI, and height-adjusted bone density measures. Additional adjustment for alcohol intake, caffeine consumption, smoking status, and estrogen supplement (female only) did not alter the results. The present study could not demonstrate linkage of BMD to chromosome 12q12-14. These findings suggest that neither the VDR gene nor other genes at this locus are likely to have a substantial impact upon bone density.
Keywords:BMD, Framingham Cohort, Linkage, VDR
Source:Calcified Tissue International
ISSN:0171-967X
Publisher:Springer Verlag (U.S.A.)
Volume:67
Number:6
Page Range:434-439
Date:1 January 2000
Official Publication:https://doi.org/10.1007/s002230001175
PubMed:View item in PubMed

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