Journal Article10.1007/S00223-007-9072-7
PTHR1 Polymorphisms Influence BMD Variation through Effects on the Growing Skeleton
Carles Vilariño-Güell,LJ Miles,Emma L. Duncan,Stuart H. Ralston,Stuart H. Ralston,Juliet E. Compston,Cyrus Cooper,Bente L. Langdahl,Alasdair MacLelland,Huibert A. P. Pols,D. M. Reid,André G. Uitterlinden,Colin D Steer,Jon H Tobias,John Wass,Matthew A. Brown,Matthew A. Brown +16 more
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TL;DR: In this article, the PTHR1 gene, including its 14 exons, their exon-intron boundaries, and 1,500 bp of its promoter region, was screened for polymorphisms by denaturing high-performance liquid chromatography (dHPLC) and sequencing in 36 osteoporosis cases.
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Abstract: We investigated whether polymorphisms in PTHR1 are associated with bone mineral density (BMD), to determine whether the association of this gene with BMD was due to effects on attainment of peak bone mass or effects on subsequent bone loss. The PTHR1 gene, including its 14 exons, their exon-intron boundaries, and 1,500 bp of its promoter region, was screened for polymorphisms by denaturing high-performance liquid chromatography (dHPLC) and sequencing in 36 osteoporotic cases. Eleven single-nucleotide polymorphisms (SNPs), one tetranucleotide repeat, and one tetranucleotide deletion were identified. A cohort of 634 families, including 1,236 men (39%) and 1,926 women (61%) ascertained with probands with low BMD (Z 5%) and the tetranucleotide repeat. In our osteoporosis families, association was noted between lumbar spine BMD and alleles of a known functional tetranucleotide repeat (U4) in the PTHR1 promoter region (P = 0.042) and between two and three marker haplotypes of PTHR1 polymorphisms with lumbar spine, femoral neck, and total hip BMD (P = 0.021-0.047). This association was restricted to the youngest tertile of the population (age 16-39 years, P = 0.013-0.048). A similar association was found for the ALSPAC cohort: two marker haplotypes of SNPs A48609T and C52813T were associated with height (P = 0.006) and total body less head BMD (P = 0.02), corrected for age and gender, confirming the family findings. These findings suggest a role for PTHR1 variation in determining peak BMD.
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Citations
Reduced bone mass in daughters of women with osteoporosis
Ego Seeman,John L. Hopper,Leon A. Bach,Mark E. Cooper,Elizabeth Parkinson,J. McKay,George Jerums +6 more
TL;DR: It is concluded that daughters of women with osteoporosis have reduced bone mass in the lumbar spine and perhaps in the femoral neck; this reduction in bone mass may put them at increased risk for fractures.
302
Suggestive linkage of the parathyroid receptor type 1 to osteoporosis
Emma L. Duncan,Matthew A. Brown,Janet S. Sinsheimer,John C. Bell,Andrew Carr,B. Paul Wordsworth,John A.H. Wass +6 more
- 01 Dec 1999
TL;DR: Investigation of the role of 23 candidate genes in the control of bone mineral density by linkage studies in families of probands with osteoporosis found suggestive evidence of linkage between BMD and PTHR1, IL‐6, and COLIIA1/VDR.
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Common variants in the region around Osterix are associated with bone mineral density and growth in childhood
Leena Peltonen,Nicholas J. Timpson,Jon H Tobias,J. Brent Richards,Nicole Soranzo,Emma L. Duncan,A. M. Sims,Pamela Whittaker,Vasudev Kumanduri,Guangju Zhai,Beate Glaser,John A. Eisman,Graeme Jones,Geoff Nicholson,Richard L. Prince,Ego Seeman,Tim D. Spector,Matthew A. Brown,George Davey-Smith,Panos Deloukas,David M. Evans +20 more
- 01 Jan 2009
Abstract: Peak bone mass achieved in adolescence is a determinant of bone mass in later life. In order to identify genetic variants affecting bone mineral density (BMD), we performed a genome-wide association study of BMD and related traits in 1518 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). We compared results with a scan of 134 adults with high or low hip BMD. We identified associations with BMD in an area of chromosome 12 containing the Osterix (SP7) locus, a transcription factor responsible for regulating osteoblast differentiation (ALSPAC: P = 5.8 × 10−4; Australia: P = 3.7 × 10−4). This region has previously shown evidence of association with adult hip and lumbar spine BMD in an Icelandic population, as well as nominal association in a UK population. A meta-analysis of these existing studies revealed strong association between SNPs in the Osterix region and adult lumbar spine BMD (P = 9.9 × 10−11). In light of these findings, we genotyped a further 3692 individuals from ALSPAC who had whole body BMD and confirmed the association in children as well (P = 5.4 × 10−5). Moreover, all SNPs were related to height in ALSPAC children, but not weight or body mass index, and when height was included as a covariate in the regression equation, the association with total body BMD was attenuated. We conclude that genetic variants in the region of Osterix are associated with BMD in children and adults probably through primary effects on growth.
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The role of GPCRs in bone diseases and dysfunctions
TL;DR: The ever-expanding number of GPCR mutation-associated diseases warrants accelerated molecular analysis, population studies, and investigation of phenotype correlation with SNPs to elucidate G PCR function in human diseases.
Site and gender specificity of inheritance of bone mineral density
Emma L. Duncan,Lon R. Cardon,Janet S. Sinsheimer,John Wass,Matthew A. Brown,Matthew A. Brown,Matthew A. Brown +6 more
- 01 Jan 2003
TL;DR: Spine BMD correlated more strongly in male‐male comparisons and hip BMD in female‐female comparisons, consistent with gender‐ and site‐specificity of BMD heritability.
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