The effect of LRP5 polymorphisms on bone mineral density is apparent in childhood
The effect of LRP5 polymorphisms on bone mineral density is apparent in childhood
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DOI：
10.1007/s00223-007-9024-2
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发表时间：
2007-07-01
影响因子：
4.2
通讯作者：
Brown, Matthew A.
中科院分区：
文献类型：
--
作者：
Koay, M. Audrey;Tobias, Jonathan H.;Brown, Matthew A.
儿童时期获得的骨量是成人骨密度(BMD)和骨质疏松风险的主要决定因素。骨积累受遗传因素的影响。激活和失活LRP5基因突变会导致极端的骨表型，而更常见的LRP5基因多态与正常的骨密度变异相关。我们的目的是验证LRP5基因多态影响儿童时期骨量获得的假设。对819名9岁的英国高加索儿童(n=429)的LRP5基因多态性与骨大小和矿化的关系进行了研究。评估了身高、体重、青春期状态(如果有)、全身和脊柱骨面积、骨矿含量(BMC)、骨密度和面积调整的骨矿含量(ABMC)。通过对年龄、性别、青春期状况和体型参数进行调整，通过线性回归评估双能X射线吸收测量仪(DXA)的基因关联性。分别有140名、79名、12名和2名女孩达到Tanner阶段I-IV，179名和32名男孩分别达到Tanner阶段I和II。LRP5基因第10外显子rs2306862(N740N)编码多态与脊柱骨密度和ABMC相关(P=0.01)，与全身骨密度和ABMC相关(P=0.04和0.03)。调整青春期阶段后，该基因多态与脊柱骨密度和ABMC之间的关联性增强(分别为P=0.002和P=0.01)。T等位基因纯合子个体的脊柱骨密度和ABMC评分高于C等位基因纯合子个体。TC杂合子个体的平均脊柱骨密度和ABMC介于TT和CC个体之间，存在明显的剂量效应。在青春期前和青春期早期儿童中，LRP5外显子10的N740N多态与脊柱骨密度和ABMC相关。这些结果表明，LRP5可能通过影响骨小梁的形成而影响儿童时期的体积骨密度。
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.