Author: Koay M.
Publisher: Springer Publishing Company
ISSN: 0171-967X
Source: Calcified Tissue International, Vol.81, Iss.1, 2007-07, pp. : 1-9
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Abstract
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</i> gene mutations elicit extreme bone phenotypes, while more common LRP5</i> polymorphisms are associated with normal variation of BMD. Our aim was to test the hypothesis that LRP5</i> gene polymorphisms influence bone mass acquisition during childhood. The association between LRP5</i> gene polymorphisms and bone size and mineralization was examined in 819 unrelated British Caucasian children (n</i> = 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</i> gene was associated with spinal BMD and aBMC (each P</i> = 0.01) and total-body BMD and aBMC (P</i> = 0.04 and 0.03, respectively). Adjusting for pubertal stage strengthened associations between this polymorphism and spinal BMD and aBMC (P</i> = 0.01 and 0.002, respectively). Individuals homozygous for the T</i> allele had greater spinal BMD and aBMC scores than those homozygous for the C</i> allele. A dose effect was apparent as the mean spinal BMD and aBMC of heterozygous TC</i> individuals were intermediate between those of their TT</i> and CC</i> counterparts. The N740N polymorphism in exon 10 of LRP5</i> 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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