Key Laboratory of Endocrinology of Ministry of Health, Department of Endocrinology, Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing 100730, China.
Eur J Endocrinol. 2013 Oct 1;169(5):629-38. doi: 10.1530/EJE-13-0441. Print 2013 Nov.
The purpose of this study was to investigate the distribution of the A986S and R990G polymorphisms of the calcium-sensing receptor (CASR) gene in the Chinese population and whether there is an association between genetic variants and the risk of developing primary hyperparathyroidism (PHPT) and its associated clinical phenotypes.
A total of 164 Chinese Han PHPT patients (M/F: 51/113) and 230 healthy controls (M/F: 50/180) were enrolled. The common clinical parameters of PHPT patients including biochemical markers, bone mineral density (BMD), kidney stone occurrence, and pathology results were analyzed. Genotyping was conducted for both the patients and controls, and it was carried out using standard procedures.
The R990G variant was more frequently present than the A986S variant in this group of Chinese PHPT patients. The R allele increased the risk of PHPT (odds ratio=1.134, 95% CI: 1.008, 1.277, and P=0.036). Patients with either the RR or RG genotype had lower blood calcium levels and higher alkaline phosphate levels than patients with the GG genotype. The lumbar BMD T-score was -2.20 (-2.63, -0.32) in patients with the GG genotype, and it was significantly lower in patients with the RR+RG genotype (-2.53 (-3.70, -1.72) P=0.036). Patients with the R allele had a significantly higher incidence of hyperplasia (25.0%) and carcinomas (7.1%) than those with the GG genotype (5.3 and 0% respectively; P=0.025). The prevalence of osteoporosis and parathyroid carcinomas was higher in Chinese PHPT patients with the R allele.
The R990G polymorphism is most frequently present in the Chinese population and among patients with PHPT. Additional studies in the Chinese population are needed to elaborate the relationship between genetics and PHPT.
本研究旨在探讨钙敏感受体（CASR）基因 A986S 和 R990G 多态性在中国人中的分布，以及遗传变异与原发性甲状旁腺功能亢进症（PHPT）及其相关临床表型的发病风险之间是否存在关联。
共纳入 164 例汉族 PHPT 患者（男/女：51/113）和 230 例健康对照者（男/女：50/180）。分析 PHPT 患者的常见临床参数，包括生化标志物、骨密度（BMD）、肾结石发生情况和病理结果。对患者和对照者进行基因分型，采用标准程序进行。
在这组中国 PHPT 患者中，R990G 变异比 A986S 变异更为常见。R 等位基因增加了 PHPT 的发病风险（比值比=1.134，95%可信区间：1.008，1.277，P=0.036）。RR 或 RG 基因型的患者血钙水平较低，碱性磷酸酶水平较高，而 GG 基因型的患者则较低。GG 基因型患者的腰椎 BMD T 评分为-2.20（-2.63，-0.32），RR+RG 基因型患者的评分明显较低（-2.53（-3.70，-1.72），P=0.036）。携带 R 等位基因的患者增生（25.0%）和癌（7.1%）的发生率明显高于 GG 基因型患者（分别为 5.3%和 0%；P=0.025）。携带 R 等位基因的中国 PHPT 患者骨质疏松症和甲状旁腺癌的患病率较高。
R990G 多态性在中国人群和 PHPT 患者中最为常见。需要在中国人中进行更多的研究，以阐述遗传与 PHPT 之间的关系。
