Karkoszka H, Chudek J, Strzelczyk P, Wiecek A, Schmidt-Gayk H, Ritz E, Kokot F
Kliniki Nefrologii, Endokrynologii i Chorób Przemjany Materii Slaskiej Akademii Medycznej w Katowicach.
Pol Merkur Lekarski. 1998 Oct;5(28):199-202.
It has been suggested that the vitamin D receptor (VDR) gene Bsml-polymorphism is a genetic determinant of bone metabolism. To test this hypothesis, the relationship between VDR genotypes, bone mineral density (baseline and after 18 months) and parameters of calcium metabolism and bone turnover were investigated prospectively in 136 haemodialyzed patients. Lumbar spine and femoral neck bone mineral density (BMD) were assessed by dual energy X-ray absorptiometry (DEXA). In addition calcium, phosphorus, 25(OH)D3, 1.25(OH)2D3, osteocalcin serum concentrations, bone alkaline phosphatase activity and intact 1, 84-PTH levels were measured. VDR genotype BB, Bb and bb were found in 24%, 46% and 30% of patients respectively. Initial BMD (g/cm2) of lumbar spine and femoral neck did not differ between genotypes, however the decrease of femoral neck BMD during 18 months of observation differ significantly (p < 0.02) between the particular genotype groups (femoral neck: BB -0.031 +/- 0.029; Bb -0.027 +/- 0.017; bb -0.017 +/- 0.019 g/cm2). Significantly lower serum level of 25OHD3 was found in patients with the BB genotype before and after 18 months of observation in comparison to the respective values obtained in bb genotype patients, (respectively, 21.0 +/- 16.8 ng/ml vs 30.8 +/- 17.9 ng/ml; p < 0.01 and 24.0 +/- 10.8 ng/ml vs 32.4 +/- 16.0 ng/ml; p < 0.02). BB genotype patients were also characterised by significantly lower serum level of 1.25(OH)2D3 both initially and after 18 month of the study (respectively in BB and bb patients 25.9 +/- 9.7 pg/ml vs 30.7 +/- 10.0 pg/ml; p < 0.02 and 18.4 +/- 12.3 pg/ml vs 24.3 +/- 13.0 pg/ml; p < 0.01). No significant differences were found in Ca, P, osteocalcin, iPTH serum concentrations and bone fraction of alkaline phosphatase activity between particular genotypes. Results from this study suggest that faster bone mineral loss and more exaggerated disturbances of vitamin D metabolism are present in haemodialyzed uraemic patients with BB than bb genotype of VDR.
有人提出维生素D受体（VDR）基因Bsml多态性是骨代谢的遗传决定因素。为了验证这一假设，我们对136例血液透析患者进行了前瞻性研究，探讨VDR基因型、骨矿物质密度（基线和18个月后）与钙代谢及骨转换参数之间的关系。采用双能X线吸收法（DEXA）评估腰椎和股骨颈的骨矿物质密度（BMD）。此外，还测量了钙、磷、25（OH）D3、1,25（OH）2D3、骨钙素血清浓度、骨碱性磷酸酶活性和完整的1,84-PTH水平。分别在24%、46%和30%的患者中发现了VDR基因型BB、Bb和bb。各基因型之间腰椎和股骨颈的初始BMD（g/cm²）无差异，但在18个月的观察期内，股骨颈BMD的下降在特定基因型组之间有显著差异（p<0.02）（股骨颈：BB -0.031±0.029；Bb -0.027±0.017；bb -0.017±0.019 g/cm²）。与bb基因型患者相比，BB基因型患者在观察18个月前后的25OHD3血清水平均显著降低（分别为21.0±16.8 ng/ml对30.8±17.9 ng/ml；p<0.01和24.0±10.8 ng/ml对32.4±16.0 ng/ml；p<0.02）。BB基因型患者在研究初始和18个月后的1,25（OH）2D3血清水平也显著较低（BB和bb患者分别为25.9±9.7 pg/ml对30.7±10.0 pg/ml；p<0.02和18.4±12.3 pg/ml对24.3±13.0 pg/ml；p<0.01）。各基因型之间的钙、磷、骨钙素、iPTH血清浓度和碱性磷酸酶活性的骨部分无显著差异。本研究结果表明，与VDR基因bb基因型的血液透析尿毒症患者相比，BB基因型患者的骨矿物质流失更快，维生素D代谢紊乱更严重。
