Cetani F, Borsari S, Vignali E, Pardi E, Picone A, Cianferotti L, Rossi G, Miccoli P, Pinchera A, Marcocci C
Department of Endocrinology and Metabolism, University of Pisa, Italy.
J Endocrinol Invest. 2002 Jul-Aug;25(7):614-9. doi: 10.1007/BF03345085.
The calcium-sensing receptor (CaR) polymorphism A986S has been found to be associated with higher serum calcium levels in normal subjects, suggesting that this amino acid change might decrease the inhibitory activity of the mutated receptor, render the parathyroid cells more prone to proliferate, and eventually increase the risk of developing primary hyperparathyroidism (PHPT). The aim of the present study was to investigate the frequency of this and other 2 known CaR polymorphisms (R990G and Q1011 E) in patients with PHPT and their effect on its phenotype. We studied 103 Italian patients with PHPT and 148 healthy Italian subjects and we compared the results in 50 pairs matched for sex, age and geographic provenience. A fragment of exon 7 of the CaR gene, containing the 3 polymorphic loci of interest (A986S, R990G, and Q1011E), was amplified by PCR and sequenced. Serum calcium and PTH levels, BMD and other biochemical and clinical parameters were evaluated. The frequency distribution of the A9865, R990G, and Q1011 E polymorphisms in the 103 PHPT patients was 39.8%, 5.8%, and 2.0%, respectively. There was no difference in the frequency of the 3 CaR polymorphisms in the 50 matched pairs of patients and controls. We found no significant difference in several clinical and biochemical parameters between PHPT patients carrying or not the 986S allele. Finally, no relationship was observed between the 986S genotype and total and ionized serum calcium in control subjects. The A986S CaR polymorphism is the most common in Italian PHPT patients and the allotype AS does not appear to play a relevant role in the pathogenesis of PHPT and its severity. The A986S polymorphism does not correlate with serum calcium levels in normal Italian subjects.
钙敏感受体（CaR）基因多态性A986S已被发现与正常受试者较高的血清钙水平相关，这表明这种氨基酸变化可能会降低突变受体的抑制活性，使甲状旁腺细胞更易于增殖，并最终增加患原发性甲状旁腺功能亢进症（PHPT）的风险。本研究的目的是调查这种以及其他两种已知的CaR基因多态性（R990G和Q1011E）在PHPT患者中的频率及其对其表型的影响。我们研究了103例意大利PHPT患者和148名健康意大利受试者，并比较了50对在性别、年龄和地理来源方面匹配的结果。通过PCR扩增包含3个感兴趣的多态性位点（A986S、R990G和Q1011E）的CaR基因外显子7片段并进行测序。评估血清钙和甲状旁腺激素水平、骨密度以及其他生化和临床参数。103例PHPT患者中A986S、R990G和Q1011E多态性的频率分布分别为39.8%、5.8%和2.0%。在50对匹配的患者和对照中，3种CaR基因多态性的频率没有差异。我们发现携带或不携带986S等位基因的PHPT患者在几个临床和生化参数上没有显著差异。最后，在对照受试者中未观察到986S基因型与总血清钙和离子化血清钙之间的关系。A986S CaR基因多态性在意大利PHPT患者中最为常见，异型AS似乎在PHPT的发病机制及其严重程度中不发挥相关作用。A986S多态性与正常意大利受试者的血清钙水平无关。
