Lorentzon M, Lorentzon R, Lerner U H, Nordström P
Sports Medicine, Department of Surgical and Perioperative Sciences, Umeå University, Sweden.
Eur J Endocrinol. 2001 Mar;144(3):257-61. doi: 10.1530/eje.0.1440257.
Bone mineral density (BMD) in adolescence is under strong genetic control. The calcium sensing receptor (CASR) is involved in the regulation of calcium homeostasis and bone resorption. The A986S polymorphism of the CASR has recently been associated with serum calcium levels, in one hitherto unconfirmed report. We investigated whether this polymorphism was related to BMD, circulating calcium and parathyroid hormone (PTH) concentrations in girls.
BMD, plasma calcium and serum PTH were measured in adolescent girls and compared with regard to CASR genotype.
In 97 healthy Caucasian girls (mean age 16.9+/-1.2 years (mean+/-s.d.)), the A and S alleles were determined using PCR with a mismatched primer and the restriction enzyme BsaHI. BMD (g/cm) of the total body, humerus, femoral neck and lumbar spine was measured using dual energy X-ray absorptiometry.
The genotype frequencies were 71% AA, 26% AS and 3% SS. The genotypes were divided into presence (29%) or absence of S allele (71%). Subjects with the S allele had higher levels of plasma calcium, corrected for albumin (2.17+/-0.06>2.14+/-0.06; P < 0.05, using independent samples t-test), lower BMD at the lumbar spine (P=0.02) and total body (P=0.04), and were significantly less physically active (2.9+/-2.6 vs 4.3+/-2.6 h/week; P=0.01) than the subjects lacking the S allele. PTH levels were not significantly different between the two allelic groups. A multiple regression analysis, including age, height, weight and physical activity, revealed that the CASR allelic variants were not independent predictors of BMD at any site measured (beta=-0.03-0.09; P>0.05). Physical activity was an independent predictor of BMD, was significantly different between the CASR genotypes, and could therefore have a role in explaining the difference in BMD between the CASR genotypes.
The CASR alleles are related to BMD, but it cannot be definitely concluded whether the CASR polymorphism has a direct influence on BMD, or whether the differences in BMD were mediated via an influence of the amount of physical activity.
青春期骨矿物质密度（BMD）受强大的基因控制。钙敏感受体（CASR）参与钙稳态调节和骨吸收。在一份尚未得到证实的报告中，CASR的A986S多态性最近与血清钙水平相关。我们调查了这种多态性是否与女孩的骨密度、循环钙和甲状旁腺激素（PTH）浓度有关。
测量青春期女孩的骨密度、血浆钙和血清PTH，并根据CASR基因型进行比较。
在97名健康的白种女孩（平均年龄16.9±1.2岁（平均值±标准差））中，使用错配引物PCR和限制性内切酶BsaHI确定A和S等位基因。使用双能X线吸收法测量全身、肱骨、股骨颈和腰椎的骨密度（g/cm）。
基因型频率为71%AA、26%AS和3%SS。将基因型分为存在S等位基因（29%）或不存在S等位基因（71%）。携带S等位基因的受试者校正白蛋白后的血浆钙水平较高（2.17±0.06>2.14±0.06；使用独立样本t检验，P<0.05），腰椎（P=0.02）和全身（P=0.04）的骨密度较低，且体力活动明显少于不携带S等位基因的受试者（2.9±2.6 vs 4.3±2.6小时/周；P=0.01）。两组等位基因的PTH水平无显著差异。包括年龄、身高、体重和体力活动在内的多元回归分析显示，CASR等位基因变异不是所测量任何部位骨密度的独立预测因子（β=-0.03-0.09；P>0.05）。体力活动是骨密度的独立预测因子，在CASR基因型之间有显著差异，因此可能在解释CASR基因型之间骨密度差异方面发挥作用。
CASR等位基因与骨密度有关，但不能确定CASR多态性是否对骨密度有直接影响，或者骨密度差异是否通过体力活动量的影响介导。
