Nagaba Y, Heishi M, Tazawa H, Tsukamoto Y, Kobayashi Y
Fourth Department of Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Am J Kidney Dis. 1998 Sep;32(3):464-9. doi: 10.1053/ajkd.1998.v32.pm9740163.
Adynamic bone disease unrelated to aluminum deposition, with low parathyroid hormone (PTH) levels, has increased in patients with end-stage renal failure. Some patients present with severe secondary hyperparathyroidism despite calcitriol administration and phosphate restriction. Because therapeutic and environmental factors are now similar among hemodialyzed patients, the variable incidence of secondary hyperparathyroidism may be caused by genetic heterogeneity. To examine this possibility, we analyzed restriction fragment length polymorphisms of the vitamin D receptor (VDR) gene in 877 Japanese hemodialysis patients. VDR allelic polymorphism was determined by the method of Morrison et al. Polymerase chain reaction (PCR) amplification and a BsmI endonuclease restriction site at the 5' end of the VDR gene defined BB (absence of restriction site on both alleles), Bb (heterozygous), or bb (restriction site on both alleles). The mean serum PTH level was lower in BB patients (86 +/- 102 pg/mL) than in bb patients (148 +/- 217 pg/mL; P < 0.05). The serum osteocalcin level was also lower in BB than in bb patients (P < 0.05). If results were re-analyzed excluding patients with a history of dialysis exceeding 10 years or those with non-insulin-dependent diabetes mellitus (NIDDM) or who had undergone parathyroidectomy, the differences in serum PTH levels were greater. However, there was no significant difference in serum PTH levels among the VDR genotypes, only for patients with NIDDM. The present study shows that patients with the b allele for the VDR gene have more severe secondary hyperparathyroidism than patients without the b allele. However, NIDDM or a long history of hemodialysis has a stronger power to influence PTH secretion.
与铝沉积无关、甲状旁腺激素（PTH）水平较低的动力缺失性骨病，在终末期肾衰竭患者中有所增加。尽管给予了骨化三醇治疗并限制了磷摄入，但仍有一些患者出现严重的继发性甲状旁腺功能亢进。由于目前血液透析患者的治疗和环境因素相似，继发性甲状旁腺功能亢进的发病率差异可能是由基因异质性引起的。为了检验这种可能性，我们分析了877例日本血液透析患者维生素D受体（VDR）基因的限制性片段长度多态性。VDR等位基因多态性采用Morrison等人的方法测定。通过聚合酶链反应（PCR）扩增以及VDR基因5'端的BsmI核酸内切酶限制性位点来确定BB（两个等位基因均无限制性位点）、Bb（杂合子）或bb（两个等位基因均有限制性位点）。BB患者的平均血清PTH水平（86±102 pg/mL）低于bb患者（148±217 pg/mL；P<0.05）。BB患者的血清骨钙素水平也低于bb患者（P<0.05）。如果重新分析结果，排除透析史超过10年的患者、非胰岛素依赖型糖尿病（NIDDM）患者或接受过甲状旁腺切除术的患者，血清PTH水平的差异会更大。然而，仅对于NIDDM患者，VDR基因型之间的血清PTH水平没有显著差异。本研究表明，VDR基因b等位基因患者的继发性甲状旁腺功能亢进比无b等位基因患者更严重。然而，NIDDM或长期血液透析对PTH分泌的影响更大。
