Hauache O M, Lazaretti-Castro M, Andreoni S, Gimeno S G, Brandão C, Ramalho A C, Kasamatsu T S, Kunii I, Hayashi L F, Dib S A, Vieira J G
Department of Medicine, Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil.
Osteoporos Int. 1998;8(3):204-10. doi: 10.1007/s001980050055.
Patients with insulin-dependent diabetes mellitus (IDDM) are at higher risk of developing osteoporosis. Among the genetic factors related to the development of osteoporosis, a possible association between vitamin D receptor (VDR) gene polymorphism and bone mineral density (BMD) has been described in some populations. We characterized the VDR gene polymorphism in a healthy adult Brazilian population and in a group of patients with IDDM and correlated these findings with densitometric values in both groups. The Brazilian population is characterized by an important racial heterogeneity and therefore is considered an ethnically heterogeneous population. We recruited 94 healthy adult Brazilian volunteers (63 women and 31 men), mean (+/- SD) age 32.4 +/- 6.5 years (range 18-49 years), and 78 patients with IDDM (33 women and 45 men) diagnosed before 18 years of age, mean (+/- SD) age 23.3 +/- 5.5 years (range 18-39 years). VDR genotype was assessed by polymerase chain reaction amplification followed by BsmI digestion on DNA isolated from peripheral blood leukocytes. Statistical analysis included Bonferroni t-test to compare densitometric values within different genotypes in both groups and multiple regression analysis of bone density adjusted for potential confounding factors. The IDDM group had a lower BMD compared with the control group. The VDR genotype distribution in the control group was 43 Bb (45.7%), 39 bb (41.5%) and 12 BB (12.8%). This distribution did not differ from that observed in the IDDM group: 39 Bb (50%), 26 bb (33.3%) and 13 BB (16.7%). In the IDDM group, patients with the Bb genotype had a higher body weight when compared with the BB genotype (p = 0.02). However, when diabetic patients were controlled for age, sex and body mass index, BB genotype was associated with a lower mean BMD at lumbar spine and femoral neck than in Bb and bb patients. BB patients had a shorter duration of IDDM than bb and Bb patients. These findings suggest a small influence of VDR gene polymorphism on BMD of a racially heterogeneous population with IDDM.
胰岛素依赖型糖尿病（IDDM）患者患骨质疏松症的风险更高。在与骨质疏松症发生相关的遗传因素中，维生素D受体（VDR）基因多态性与骨密度（BMD）之间的可能关联已在一些人群中得到描述。我们对一组健康的巴西成年人群和一组IDDM患者的VDR基因多态性进行了特征分析，并将这些结果与两组的骨密度测量值相关联。巴西人群的特点是种族异质性显著，因此被认为是一个种族多样化的人群。我们招募了94名健康的巴西成年志愿者（63名女性和31名男性），平均（±标准差）年龄为32.4±6.5岁（范围18 - 49岁），以及78名18岁之前被诊断为IDDM的患者（33名女性和45名男性），平均（±标准差）年龄为23.3±5.5岁（范围18 - 39岁）。通过聚合酶链反应扩增，随后对从外周血白细胞中分离的DNA进行BsmI消化来评估VDR基因型。统计分析包括Bonferroni t检验，以比较两组不同基因型之间的骨密度测量值，以及对骨密度进行多元回归分析，以调整潜在的混杂因素。与对照组相比，IDDM组的骨密度较低。对照组的VDR基因型分布为43例Bb（45.7%）、39例bb（41.5%）和12例BB（12.8%）。这种分布与IDDM组中观察到的分布没有差异：39例Bb（50%）、26例bb（33.3%）和13例BB（16.7%）。在IDDM组中，Bb基因型的患者与BB基因型的患者相比体重更高（p = 0.02）。然而，当对糖尿病患者的年龄、性别和体重指数进行控制后，BB基因型与腰椎和股骨颈的平均骨密度低于Bb和bb基因型的患者相关。BB基因型的患者IDDM病程比bb和Bb基因型的患者短。这些发现表明VDR基因多态性对具有IDDM的种族多样化人群的骨密度有较小影响。
