The effect of LRP5 polymorphisms on bone mineral density is apparent in childhood

Koay, M. A., Tobias, J. H., Leary, S. D., Steer, C. D., Vilariño-Güell, C., & Brown, M.A. (2007) The effect of LRP5 polymorphisms on bone mineral density is apparent in childhood. Calcified Tissue International, 81(1), pp. 1-9.

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Bone mass acquired during childhood is the primary determinant of adult bone mineral density (BMD) and osteoporosis risk. Bone accrual is subject to genetic influences. Activating and inactivating LRP5 gene mutations elicit extreme bone phenotypes, while more common LRP5 polymorphisms are associated with normal variation of BMD. Our aim was to test the hypothesis that LRP5 gene polymorphisms influence bone mass acquisition during childhood. The association between LRP5 gene polymorphisms and bone size and mineralization was examined in 819 unrelated British Caucasian children (n = 429 boys) aged 9 years. Height, weight, pubertal status (where available), total-body and spinal bone area, bone mineral content (BMC), BMD, and area-adjusted BMC (aBMC) were assessed. Dual-energy X-ray absorptiometry (DXA)-gene associations were assessed by linear regression, with adjustment for age, gender, pubertal status, and body size parameters. There were 140, 79, 12, and 2 girls who achieved Tanner stages I-IV, respectively, and 179 and 32 boys who achieved Tanner stages I and II, respectively. The rs2306862 (N740N) coding polymorphism in exon 10 of the LRP5 gene was associated with spinal BMD and aBMC (each P = 0.01) and total-body BMD and aBMC (P = 0.04 and 0.03, respectively). Adjusting for pubertal stage strengthened associations between this polymorphism and spinal BMD and aBMC (P = 0.01 and 0.002, respectively). Individuals homozygous for the T allele had greater spinal BMD and aBMC scores than those homozygous for the C allele. A dose effect was apparent as the mean spinal BMD and aBMC of heterozygous TC individuals were intermediate between those of their TT and CC counterparts. The N740N polymorphism in exon 10 of LRP5 was associated with spinal BMD and aBMC in pre- and early pubertal children. These results indicate that LRP5 influences volumetric bone density in childhood, possibly through effects on trabecular bone formation.

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ID Code: 87985
Item Type: Journal Article
Refereed: Yes
Additional Information: No file attached.
Keywords: Association, Bone mineral density, Growth, Height, LRP5, age distribution, allele, article, body height, body mass, body size, body weight, bone densitometry, bone density, bone mass, bone mineral, bone mineralization, cancer staging, Caucasian, childhood, DNA polymorphism, dual energy X ray absorptiometry, exon, female, gene, genetic association, haplotype, heterozygosity, homozygosity, human, linear regression analysis, LRP5 gene, male, phenotype, priority journal, puberty, school child, scoring system, sex ratio, volumetry, Age Factors, Child, Cohort Studies, Genotype, Haplotypes, Humans, LDL-Receptor Related Proteins, Models, Genetic, Models, Statistical, Polymorphism, Genetic
DOI: 10.1007/s00223-007-9024-2
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 23:22
Last Modified: 18 Oct 2015 22:53

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