The Clinical Phenotypes in Chinese Primary Hyperparathyroidism Patients was Associated with Calcium-sensing Receptor Gene R 990 G Polymorphisms

Objective: 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. Methods: 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 in both patients and controls and performed using standard procedures. Results: R990G was more frequent than A986S in this group of Chinese PHPT patients. The R allele increased the risk of PHPT (OR=1.134, 95% CI:1.008, 1.277, ∗ Key Laboratory of Endocrinology of Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College ,Chinese Academy of Medical Sciences, Beijing, 100730, China. Email: xiaopingxing@126.com.Tel:86-10-69155084. Page 1 of 29 Accepted Preprint first posted on 14 August 2013 as Manuscript EJE-13-0441 Copyright © 2013 European Society of Endocrinology. 2 P=0.036). Patients with genotypes of either RR or RG, had lower blood calcium levels and higher ALP levels than patients with GG. The lumbar BMD T-score was -2.20 (-2.63, -0.32) in patients with GG and significantly lower in RR+RG patients (-2.53 [-3.70, -1.72] P=0.036). The patients with the R allele had a significantly higher incidence of hyperplasia (25.0%) and carcinoma (7.1%) than patients with the GG genotype (5.3% and 0%, respectively; P=0.025). Osteoporosis and parathyroid carcinoma were higher in Chinese PHPT patients with the R allele. Conclusion: R990G was the most frequent polymorphism 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.