Donáth J, Speer G, Poór G, Gergely P, Tabák A, Lakatos P
National Institute of Rheumatology and Physiotherapy, Budapest, Hungary.
Rheumatology (Oxford). 2004 Jun;43(6):692-5. doi: 10.1093/rheumatology/keh162. Epub 2004 Mar 2.
The significance of genetic polymorphisms in the development of Paget's disease of bone is unclear at present.
We analysed the BsmI polymorphism of the vitamin D receptor (VDR) gene, the PvuII and XbaI polymorphisms of the oestrogen receptor-alpha (ER alpha) gene, and the A986S polymorphism of the calcium-sensing receptor (CaSR) gene in 69 pagetic patients and 120 healthy subjects. We also examined the relationship of these polymorphisms with lumbar spine and femoral neck BMD as well as with biochemical parameters (serum alkaline phosphatase, osteocalcin and parathyroid hormone) in Paget's disease.
The XbaI and PvuII genotype distributions of the ER alpha gene were significantly different between patients with Paget's disease and control subjects (P<0.001). Also, the CaSR A986S genotype frequency was significantly different between pagetic patients and controls (P<0.01). No significant effect of gene polymorphisms on BMD or biochemical parameters of bone turnover was observed.
Our results suggest that the ER alpha PvuII/XbaI and CaSR A986S polymorphisms may contribute to genetic susceptibility to Paget's disease. However, further studies are required to investigate the underlying pathomechanism and to replicate the associations.
目前骨Paget病发生过程中基因多态性的意义尚不清楚。
我们分析了69例Paget病患者和120名健康受试者维生素D受体（VDR）基因的BsmI多态性、雌激素受体α（ERα）基因的PvuII和XbaI多态性以及钙敏感受体（CaSR）基因的A986S多态性。我们还研究了这些多态性与Paget病患者腰椎和股骨颈骨密度以及生化参数（血清碱性磷酸酶、骨钙素和甲状旁腺激素）之间的关系。
Paget病患者与对照受试者之间ERα基因的XbaI和PvuII基因型分布存在显著差异（P<0.001）。此外，Paget病患者与对照者之间CaSR A986S基因型频率也存在显著差异（P<0.01）。未观察到基因多态性对骨密度或骨转换生化参数有显著影响。
我们的结果表明，ERα PvuII/XbaI和CaSR A986S多态性可能与Paget病的遗传易感性有关。然而，需要进一步研究来探讨潜在的发病机制并重复这些关联。
