van der Sluis I M, de Muinck Keizer-Schrama S M P F, Krenning E P, Pols H A P, Uitterlinden A G
Department of Pediatrics, div. Endocrinology, Sophia Children's Hospital, 3000 CB Rotterdam, The Netherlands.
Calcif Tissue Int. 2003 Oct;73(4):332-8. doi: 10.1007/s00223-002-2130-2. Epub 2003 Jul 24.
Peak bone mass is considered to be under strong genetic control. We studied the association among anthropometry, bone density and vitamin D receptor (VDR) genotype in an ethnically homogeneous group of 148 Caucasian children and young adults. Bone density was measured by dual energy X-ray absorptiometry (DXA) and VDR genotype was determined by a direct haplotyping procedure of the BsmI, ApaI, and TaqI restriction fragment length polymorphisms. A second DXA measurement was made after approximately 4 years. Results are expressed as age- and sex-adjusted standard deviation scores (SDS). Previously, the collagen IA1 Sp1 polymorphism was studied in this population. We found VDR genotype to be associated with a 0.4 SDS increased height per allele copy of haplotype '3' (P = 0.04) and a 0.4 SDS increased width of the lumbar vertebral body in the haplotype '3' allele carriers (P = 0.05). We observed a trend towards a 0.3 SDS decreased bone mineral apparent density of lumbar spine (BMAD) per copy of haplotype '3' allele (P = 0.10). In contrast, no association with areal bone mineral density (BMD) was observed. In the follow-up analyses, no differences in height or bone gain among the VDR genotypes were demonstrated. By combining the risk alleles of VDR and collagen IA1 Sp1 genotype, an additive genotype effect on height (P = 0.006) and vertebral body width (P = 0.001) was found. In this exploratory study we found VDR genotype to be associated with frame size and BMAD. The VDR genotype effects on stature and bone size seem to neutralize the effect on areal BMD.
峰值骨量被认为受到强大的基因控制。我们在一个由148名白种儿童和青年组成的种族同质群体中研究了人体测量学、骨密度与维生素D受体（VDR）基因型之间的关联。通过双能X线吸收法（DXA）测量骨密度，并通过对BsmI、ApaI和TaqI限制性片段长度多态性进行直接单倍型分析程序来确定VDR基因型。大约4年后进行了第二次DXA测量。结果以年龄和性别调整后的标准差分数（SDS）表示。此前，在该人群中研究了胶原蛋白IA1 Sp1多态性。我们发现VDR基因型与单倍型“3”的每个等位基因拷贝使身高增加0.4 SDS相关（P = 0.04），并且在单倍型“3”等位基因携带者中，腰椎椎体宽度增加0.4 SDS（P = 0.05）。我们观察到一种趋势，即单倍型“3”等位基因的每个拷贝使腰椎骨矿物质表观密度（BMAD）降低0.3 SDS（P = 0.10）。相比之下，未观察到与面积骨矿物质密度（BMD）的关联。在后续分析中，未证明VDR基因型之间在身高或骨量增加方面存在差异。通过结合VDR和胶原蛋白IA1 Sp1基因型的风险等位基因，发现对身高（P = 0.006）和椎体宽度（P = 0.001）有累加基因型效应。在这项探索性研究中，我们发现VDR基因型与体格大小和BMAD相关。VDR基因型对身高和骨大小的影响似乎抵消了对面积BMD的影响。
