PTHR1 polymorphisms influence BMD variation through effects on the growing skeleton

Vilariño-Güell, Carles, Miles, Lisa J., Duncan, Emma L., Ralston, Stuart H., Compston, Juliet E., Cooper, Cyrus, Langdahl, Bente L., MacLelland, Alasdair, Pols, Huibert A., Reid, David M., Uitterlinden, André G., Steer, Colin D., Tobias, Jon H., Wass, John A.H., & Brown, Matthew A. (2007) PTHR1 polymorphisms influence BMD variation through effects on the growing skeleton. Calcified Tissue International, 81(4), pp. 270-278.

View at publisher


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< -2.0) and the Children in Focus subset of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (785 unrelated individuals, mean age 118 months), were genotyped for the five most informative SNPs (minor allele frequency >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.

Impact and interest:

13 citations in Scopus
Search Google Scholar™
10 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 87986
Item Type: Journal Article
Refereed: Yes
Keywords: Bone mineral density, Polymorphism, PTHR1, Skeleton, gene product, parathyroid hormone receptor 1, adolescent, adult, article, bone density, bone development, bone mass, child, cohort analysis, controlled study, exon, female, femur neck, gene deletion, gene sequence, genetic association, genetic polymorphism, genetic variability, genotype, groups by age, haplotype, high performance liquid chromatography, hip, human, human experiment, lumbar spine, normal human, osteolysis, priority journal, promoter region, sequence analysis, single nucleotide polymorphism, Alleles, Bone and Bones, Cohort Studies, DNA Primers, Exons, Genetic Markers, Haplotypes, Humans, Introns, Linkage Disequilibrium, Nucleic Acid Amplification Techniques, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Promoter Regions (Genetics), Receptor, Parathyroid Hormone, Type 1, Sequence Analysis, DNA, Tandem Repeat Sequences
DOI: 10.1007/s00223-007-9072-7
ISSN: 0171-967X
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 01 Oct 2015 23:24
Last Modified: 24 Mar 2016 05:23

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page