甲状旁腺素和维生素D受体基因多态对糖尿病患者骨密度的影响

Effect of parathyroid hormone and vitamin D receptor gene polymorphisms on bone mineral density in the subjects with diabetes mellitus

目的探讨甲状旁腺素（PTH）基因多态性与中国北方汉族人糖尿病患者骨密度的关系，联合分析维生素D受体（VDR）基因和PTH基因多态性与骨密度的相关性。方法选自青岛市内分泌糖尿病医院1998年1月～2002年1月住院的糖尿病患者，运用聚合酶链反应限制性片段长度多态性（PCR—RFLP）技术检测了1型糖尿病（T1DM）组54例，2型糖尿病（T2DM）组104例，健康对照（CON）组102例，260例中国北方汉族人PTH基因多态性；采用双能x线吸收法骨密度仪（DEXA）测量骨密度。结果校正年龄和BMI后，1型糖尿病组腰椎、股骨颈骨密度低于对照组（P〈0．05）；2型糖尿病组与对照组相比，骨密度差异无显著性（P〉0．05）；甲状旁腺素（BSTBI位点）基因型和等位基因分布频率在1型糖尿病组、2型糖尿病组与对照组间差异无显著性（P〉0．05）；在对照组及2型糖尿病组，BB基因型者腰椎（L24）和股骨颈部位骨密度显著高于Bb／bb基因型（P〈0．05）；在1型糖尿病组，BB基因型仅腰椎L：。部位骨密度高于Bb／bb基因型（P〈0．05）；联合VDR基因多态（ApaI酶切位点）分析结果表明，Bbaa基因型在腰椎和股骨颈骨密度低于其他基因型（P〈0．05）。结论糖尿病患者PTH基因多态性（BSTB1位点）可能是预测骨量减少、骨质疏松易感性的遗传标志。联合VDR基因多态（ApaI酶切位点）有助于识别糖尿病患者发生骨质疏松的高危人群。

Objective To evaluate the effect of parathyroid hormone gene polymorphisms on bone mineral density（BMD） and osteopenia/osteoporosis of diabetic patients of indigenous Han of north Chinese. To analyse the influence of vitamin D receptor （VDR） gene polymophism on the correlation of PTH gene polymorphism with BMD. Methods Diabetic patients （diabetic group） were selected from Endocrinology and Diabetes Hospital of Qingdao between January 1998 and January 200：2. The 158 cases with diabetes mellitus,includiug 54 with type 1 diabetes mellitus （T1DM group） and 104 with type 2 diabetes mellitus （T2DM group）,and 102 healthy controls （CON group）. Polymorphism of parathyroid hormone gene was determined by PCR-RFLP method. Bone mineral density （BMD） was measured by dual-energy （-ray absorptiometry（ DEXA）. Results After correcting for age and BMI, Bone mineral density was lower at the lumbar spine and femoral neck in subjects with type 1 diabetes compared with control group（P 〈 0. 05 ） , and was still significantly lower than that of control group （ P 〈 0. 05 ） ; BMD was not significantly different in subjects with type 2 diabetes compared with control group（ P 〉 0.05 ）. There was no significant difference in the distrubution of genotypes and allele frequencies of PTH between the type 1 diabetic,type 2 diabetic and control groups（P 〉 0.05）. Subjects with ＂BB＂ genotype had higher BMD at lumbar spine and femoral neck than those with ＂Bb/bb＂ genotype in control and type 2 diabetic group （ P 〈 0.05 ） , respectively. In type 1 diabetic group,subjects with ＂BB＂ genotype had higher BMD only at the lumbar spine than those with ＂Bb/ bb＂ genotype（P 〈0. 05）. Combined analyse of the association of PTH and VDR gene polymorphisms with osteopenia/osteoporosis showed that subjects with ＂Bbaa＂ genotype had significantly lower BMD at femoral neck and lumbar spine than those with other genotypes in diabetic group （ P 〈 0. 05 ）. Conclusions In diabetic patients,BST B 1 polymorphism of PTH gene would be a useful genetic marker for lower BMD and the susceptibility to osteoporosis. Combined analyse of the association of PTH and VDR gene polymorphisms may provide a tool to identify, more precisely, diabetic patients at risk of developing osteopenia or osteoporosis.