Carling T, Rastad J, Akerström G, Westin G
Department of Surgery, Uppsala University Hospital, Sweden.
J Clin Endocrinol Metab. 1998 Jul;83(7):2255-9. doi: 10.1210/jcem.83.7.4862.
Calcitriol, via its receptor (VDR) is a main regulator of PTH secretion and parathyroid cell proliferation. Recently, marked overrepresentation of the polymorphic VDR alleles b, a, and T was found in patients with primary hyperparathyroidism (pHPT), which suggests pathogenic importance in the disease. Using the ribonuclease protection assay, relative VDR and PTH messenger ribonucleic acid (mRNA) levels of parathyroid adenomas from 42 patients with sporadic pHPT were related to these VDR polymorphisms. The tumors of patients homozygous for the b, a, or T alleles demonstrated significantly lower VDR and higher PTH mRNA levels than those exhibiting the BB, AA, or tt genotypes (P < 0.0001-0.02), whereas heterozygotes had intermediate values. A similar discrepancy was found when comparing the baT and non-baT haplotypes (0.042 +/- 0.005 vs. 0.064 +/- 0.004 for VDR; 34.4 +/- 3.7 vs. 21.6 +/- 2.2 for PTH; both P < 0.005). The lower VDR mRNA levels associated with the b, a, and T alleles may affect the calcitriol-mediated control of parathyroid function and thereby contribute to the development of sporadic pHPT.
骨化三醇通过其受体(维生素D受体,VDR)是甲状旁腺激素(PTH)分泌和甲状旁腺细胞增殖的主要调节因子。最近,在原发性甲状旁腺功能亢进症(pHPT)患者中发现多态性VDR等位基因b、a和T明显过度表达,这表明其在该疾病中具有致病重要性。采用核糖核酸酶保护试验,对42例散发性pHPT患者甲状旁腺腺瘤的相对VDR和PTH信使核糖核酸(mRNA)水平与这些VDR多态性进行相关性分析。b、a或T等位基因纯合子患者的肿瘤,其VDR mRNA水平显著低于表现为BB、AA或tt基因型的患者,而PTH mRNA水平则更高(P < 0.0001 - 0.02),杂合子则处于中间值。比较baT和非baT单倍型时也发现了类似差异(VDR分别为0.042 ± 0.005和0.064 ± 0.004;PTH分别为34.4 ± 3.7和21.6 ± 2.2;两者P < 0.005)。与b、a和T等位基因相关的较低VDR mRNA水平可能会影响骨化三醇介导的甲状旁腺功能控制,从而促进散发性pHPT的发生。