Lau Helen H L, Ng Mandy Y M, Cheung William M W, Paterson Andrew D, Sham Pak C, Luk Keith D K, Chan Vivian, Kung Annie W C
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.
J Bone Miner Metab. 2006;24(3):226-34. doi: 10.1007/s00774-005-0676-6.
Bone mineral density (BMD), an important risk factor for osteoporosis, is a complex trait likely affected by multiple genes. The linkage and/or association of 13 polymorphic loci of seven candidate genes (estrogen receptor alpha [ERalpha] and beta [ERbeta], calcium-sensing receptor, vitamin D receptor, collagen type 1alpha1, low-density lipoprotein [LDL] receptor-related protein 5 [LRPS], and transforming growth factor beta1) were evaluated in 177 southern Chinese pedigrees of 674 subjects, with each pedigree identified through a proband having a BMD Z score of -1.28 or less at the hip or spine. A suggestive linkage was detected between the IVS1-351A/G polymorphism of ERalpha and spine BMD, and between the 1082G/A, 1730G/A, and D14S1026 polymorphisms of ERbeta and BMD at both spine and hip. The quantitative transmission disequilibrium test (QTDT) detected total family association between 1730G/A of ERbeta and BMD at spine and hip; between D14S1026 of ERbeta and hip BMD; and between the 266A/G and 2220C/T polymorphisms of LRP5 and hip BMD. Similar total family associations were detected when only the females were analyzed. In addition, the IVS1-397T/C polymorphism of ERalpha was associated with spine BMD, and the 266A/G and 2220C/T polymorphisms of LRP5 were associated with femoral neck BMD in the females. A within-family association was detected with the IVS1-397T/C polymorphism of ERalpha, and the 266A/G and 2220C/T polymorphisms of LRP5 in the females. The effect of each polymorphism on BMD variance ranged from 1% to 4%. In conclusion, ERalpha, ERbeta and LRP5 are important candidate genes determining BMD variation, especially in females.
骨密度（BMD）是骨质疏松症的一个重要风险因素，是一种可能受多个基因影响的复杂性状。在177个中国南方家系的674名受试者中，评估了7个候选基因（雌激素受体α[ERα]和β[ERβ]、钙敏感受体、维生素D受体、Ⅰ型胶原α1、低密度脂蛋白[LDL]受体相关蛋白5[LRP5]和转化生长因子β1）的13个多态性位点的连锁和/或关联，每个家系通过一名先证者确定，该先证者在髋部或脊柱的骨密度Z评分≤-1.28。在ERα的IVS1-351A/G多态性与脊柱骨密度之间，以及在ERβ的1082G/A、1730G/A和D14S1026多态性与脊柱和髋部骨密度之间检测到提示性连锁。定量传递不平衡检验（QTDT）检测到ERβ的1730G/A与脊柱和髋部骨密度之间、ERβ的D14S1026与髋部骨密度之间以及LRP5的266A/G和2220C/T多态性与髋部骨密度之间存在全家族关联。仅分析女性时，也检测到了类似的全家族关联。此外，ERα的IVS1-397T/C多态性与脊柱骨密度相关，LRP5的266A/G和2220C/T多态性与女性股骨颈骨密度相关。在女性中，检测到ERα的IVS1-397T/C多态性以及LRP5的266A/G和2220C/T多态性存在家系内关联。每个多态性对骨密度变异的影响范围为1%至4%。总之，ERα、ERβ和LRP5是决定骨密度变异的重要候选基因，尤其是在女性中。
