Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation
Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation
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DOI：
10.1359/jbmr.2001.16.2.371
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发表时间：
2001-02-01
影响因子：
6.2
通讯作者：
Spector, TD
中科院分区：
文献类型：
--
作者：
Hunter, D;De Lange, M;Spector, TD
一项经典的双胞胎研究被用来评估遗传和环境因素对骨代谢、钙稳态和调节它们的激素的相对作用。进一步研究了遗传效应是否依赖于绝经。受试者为2136对成年双胞胎（98.3%为女性）：384对单卵（MZ）和684对双卵（DZ）双胞胎。计算组内相关系数，用最大似然模型拟合估计遗传和环境方差分量。所有评估变量的组内相关性在同卵双生子中较高。根据骨代谢和钙稳态调节激素模型拟合的遗传率（95% CI）为：甲状旁腺激素（PTB）60%（54-65%），25-羟基维生素D [25（OH）D] 43%（28-57%），1，25-羟基维生素D [1，25（OH）] 65%（53-74%）;和维生素D结合蛋白62%（56-66%）。骨形成标志物的遗传率（95% CI）也进行了评估：骨特异性碱性磷酸酶（BSAP），74%（67-80%），骨钙素，29%（14-44%），骨吸收标志物脱氧吡啶啉（DPD），58%（52-64%）;测定24 h尿钙、肌酐（Cr），52%（41-61%）。遗传影响的大小与绝经期的大多数变量不同。这项研究为遗传因素在决定骨吸收和形成、钙排泄以及调节这些过程的激素方面的重要性提供了证据。它首次显示了绝经前妇女骨吸收和PTH，维生素D代谢和钙排泄的调节的明确遗传效应。控制骨激素和标记物的基因可能是有用的治疗和诊断靶点。
A classical twin study was performed to assess the relative contribution of genetic and environmental factors to bone metabolism, calcium homeostasis, and the hormones regulating them. It was examined further whether the genetic effect is menopause dependent. The subjects were 2136 adult twins (98.3% female): 384 monozygotic (MZ) and 684 dizygotic (DZ) twin pairs. The intraclass correlations mere calculated, and maximum likelihood model fitting was used to estimate genetic and environmental variance components. The intraclass correlations for all of the variables assessed were higher in MZ twin pairs. The heritabilities (95% CIs) obtained from model fitting for hormones regulating bone metabolism and calcium homeostasis were parathyroid hormone (PTB), 60% (54-65%); 25-hydroxyvitamin D [25(OH)D]; 43% (28-57%), 1,25-hydroxyvitamin D [1,25(OH)], 65% (53-74%); and vitamin D binding protein 62% (56-66%). The heritabilities (95% CIs) for markers of bone formation also were assessed; bone-specific alkaline phosphatase (BSAP), 74% (67-80%), and osteocalcin, 29% (14-44%); marker of bone resorption deoxypyridinoline (DPD), 58% (52-64%); and measure of calcium homeostasis 24 h urine calcium, creatinine (Cr), 52% (41-61%). The magnitude of genetic influence differed with menopause for most variables. This study provides evidence for the importance of genetic factors in determining bone resorption and formation, calcium excretion, and the hormones regulating these processes. It shows for the first time a clear genetic effect on bone resorption in premenopausal women and the regulation of PTH, vitamin D metabolism, and calcium excretion. The genes controlling bone hormones and markers are likely to be useful therapeutic and diagnostic targets.