scholarly journals Clinical phenotypes of Chinese primary hyperparathyroidism patients are associated with the calcium-sensing receptor gene R990G polymorphism

2013 ◽  
Vol 169 (5) ◽  
pp. 629-638 ◽  
Author(s):  
Guiyan Han ◽  
Ou Wang ◽  
Min Nie ◽  
Yan Zhu ◽  
Xunwu Meng ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Chinese Population ◽  
Receptor Gene ◽  
Mineral Density ◽  
Calcium Sensing Receptor ◽  
Chinese Han ◽  
Blood Calcium ◽  
Clinical Phenotypes ◽  
Calcium Sensing ◽  
Standard Procedures

ObjectiveThe 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.MethodsA 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.ResultsThe 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, andP=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 BMDT-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.ConclusionThe 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.

scholarly journals Cinacalcet Treatment of Primary Hyperparathyroidism

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
H. M. Rothe ◽  
O. Liangos ◽  
P. Biggar ◽  
A. Petermann ◽  
M. Ketteler
Keyword(s):  
Primary Hyperparathyroidism ◽  
Stone Formation ◽  
Receptor Gene ◽  
Calcium Excretion ◽  
Mineral Density ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
First Choice ◽  
Patient Subgroups ◽  
Urine Calcium Excretion

Although parathyroidectomy remains the only curative approach to most primary hyperparathyroidism cases, medical treatment with cinacalcet HCl has been proven to be a reasonable alternative for several patient subgroups. Cinacalcet almost always controls hypercalcemia and hypophosphatemia sufficiently. PTH levels are lowered, and cognitive parameters improve. While an increase in bone mineral density DEXA scan scores was not demonstrated in cinacalcet trials, the same applies to more than half of patients after parathyroidectomy. Medical therapy should be first choice in patients with hyperplasia in all glands rather than an isolated adenoma (10–15%), patients with persisting HPT following unsuccessful surgery or inoperable cases due to comorbidities, and patients detected in lab screens for hypercalcemia before developing symptoms who should be treated early but are usually reluctant to undergo surgery. Nephrolithiasis was not found to occur more frequently in cinacalcet trial groups, but urine calcium excretion as one major risk factor of this complication of primary HPT may increase on cinacalcet. Patients carrying the rs1042636 polymorphism of the calcium-sensing receptor gene respond more sensitively to cinacalcet and have a higher risk of calcium stone formation. Cinacalcet is usually administered twice daily but three or four doses per day should be discussed to mimic the beneficial pulsatile PTH-pattern.

scholarly journals Atypical Presentation of Familial Hypocalciuric Hypercalcemia: Case Report

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A182-A183
Author(s):  
Dalal S Ali ◽  
Karel Dandurand ◽  
Aliya Aziz Khan
Keyword(s):  
Vitamin D ◽  
Primary Hyperparathyroidism ◽  
Dna Analysis ◽  
Receptor Gene ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Calcium Sensing Receptor ◽  
Clearance Ratio ◽  
Subtotal Parathyroidectomy ◽  
Casr Gene ◽  
Calcium Sensing

Abstract Background: Differentiation between familial hypocalciuric hypercalcemia (FHH) and primary hyperparathyroidism (PHPT) can be challenging in certain cases in the absence of DNA analysis of the calcium sensing receptor gene. The distinction between those two clinical entities with overlapping biochemical features therefore relies on the calcium to creatinine clearance ratio (CCCR), which is expected to be low in FHH (<0.01 in 80% of cases and between 0.01 and 0.02 in approximately 20% of patients)1. Patients with PHPT usually have a CCCR of>= 0.02. A lower CCCR between 0.01 and 0.02 can be seen in approximately 20% of patients1,2and is more commonly seen in the presence of vitamin D insufficiency, impaired renal function, low calcium intake or being of African descent. It is advised to stop drugs which can contribute to hypercalcemia and lower the CCCR such as thiazide diuretics prior to evaluating the CCCR. Clinical Case: A 56-year-old lady was referred for evaluation of persistent hypercalcemia post parathyroidectomy and fatigue. She had mildly elevated ionized serum calcium (iCa) and a mid-normal PTH with a CCCR of 0.024. She had a normal BMD with no prior fragility fractures and passed a kidney stone prior to her presentation. Physical exam was unremarkable. She had previously travelled to Tampa and had a subtotal parathyroidectomy 3 glands (RU, LU, RL) for a possible diagnosis of PHPT, tissue biopsy showed hyperplastic parathyroids. Her MEN1 gene analysis was negative for MEN1 mutation and MRI of the abdomen was unremarkable. Her mother had a diagnosis of PHPT and osteoporosis. The iCa remained mildly elevated at 1.43 mmol/L (1.15–1.3) with a 24 hr urinary CCCR at 0.024 and a mid-normal PTH of 4.4 pmol/L (1.6–6.9). Her eGFR was 104 mls/min, 25 vitamin D 82 nmol/L (75–250), 1,25 dihydroxy vitamin D 122 pmol/L (60–206), PO4 0.90 mmol/L (0.8–1.45) and alkaline phosphatase 46 U/L (35–120) were all normal. She continued to have mild symptoms of hypercalcemia and her bone scan was negative for underlying skeletal pathology. DNA studies for mutations in the CaSR gene were completed. This confirmed the presence of a heterozygous loss of function mutation in the CASR gene at c493-2A>G which appears to be pathogenic. Conclusion: The CCCR is useful in differentiating PHPT from FHH however in certain cases of FHH the CCCR may be higher then expected and we have now confirmed the presence of FHH with a molecular diagnosis in a patient with a CCCR as high as 0.02. References: 1 Gunn, IR, Gaffney, D. Clinical and laboratory features of calcium-sensing receptor disorders: a systematic review. Ann Clin Biochem 2004; 41:441–58 2 Stephen J. Marx, Letter to the Editor: Distinguishing Typical Primary Hyperparathyroidism From Familial Hypocalciuric Hypercalcemia by Using an Index of Urinary Calcium, The Journal of Clinical Endocrinology & Metabolism, 2015

Risk of nephrolithiasis in primary hyperparathyroidism is associated with two polymorphisms of the calcium-sensing receptor gene

2014 ◽  
Vol 28 (1) ◽  
pp. 67-72 ◽  
Author(s):  
Giuseppe Vezzoli ◽  
Alfredo Scillitani ◽  
Sabrina Corbetta ◽  
Annalisa Terranegra ◽  
Elena Dogliotti ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Receptor Gene ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Calcium Sensing Receptor Gene

scholarly journals Primary Hyperparathyroidism and the Presence of Kidney Stones Are Associated with Different Haplotypes of the Calcium-Sensing Receptor

2007 ◽  
Vol 92 (1) ◽  
pp. 277-283 ◽  
Author(s):  
Alfredo Scillitani ◽  
Vito Guarnieri ◽  
Claudia Battista ◽  
Simona De Geronimo ◽  
Lucia Anna Muscarella ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Single Nucleotide Polymorphisms ◽  
Primary Hyperparathyroidism ◽  
Bone Mineral ◽  
Kidney Stones ◽  
Nucleotide Polymorphisms ◽  
Mineral Density ◽  
Calcium Sensing Receptor ◽  
Single Nucleotide ◽  
Calcium Sensing

Abstract Introduction: Three single-nucleotide polymorphisms in the calcium-sensing receptor gene (CASR) encoding the missense substitutions A986S, R990G, and Q1011E have been associated with normal variation in extracellular calcium homeostasis, both individually and in haplotype combination. The aim of this study was to examine haplotype associations in primary hyperparathyroidism (PHPT). Patients and Methods: Patients with sporadic PHPT (n = 237) were recruited from endocrine clinics and healthy controls (n = 433) from a blood donor clinic, and levels of serum calcium, albumin, and PTH were measured. In PHPT patients, urinary calcium/creatinine clearances and bone mineral density at spine and femoral neck were measured and the presence of kidney stones and vertebral fractures identified. The CASR single-nucleotide polymorphisms were haplotyped by allele-specific sequencing. Results: Four haplotypes (ARQ, SRQ, AGQ, and ARE) of eight were observed, in keeping with significant linkage disequilibrium, but haplotype frequencies did not show significant Hardy-Weinberg disequilibrium. The SRQ haplotype was more common in PHPT (125 of 474 alleles) than in controls (170 of 866 alleles, P = 0.006) and showed a significant (P = 0.006) gene-dosage effect. There was no significant association between haplotype and bone mineral density or fractures, but association with kidney stones was significant (P = 0.0007). In the stone-forming subgroup, the SRQ haplotype was underrepresented and AGQ overrepresented. Patients bearing the AGQ haplotype had an odds ratio of 3.8 (95% confidence interval, 1.30–11.3) for presentation with renal stones compared with the rest. Conclusion: Our data indicate that the CASR SRQ haplotype is significantly associated with PHPT in our population. Within the PHPT patient population, the AGQ haplotype is significantly associated with kidney stones.

scholarly journals R990G polymorphism of the calcium-sensing receptor and renal calcium excretion in patients with primary hyperparathyroidism

2006 ◽  
Vol 155 (5) ◽  
pp. 687-692 ◽  
Author(s):  
S Corbetta ◽  
C Eller-Vainicher ◽  
M Filopanti ◽  
P Saeli ◽  
G Vezzoli ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Urinary Calcium ◽  
Calcium Excretion ◽  
Calcium Sensing Receptor ◽  
Gene Encoding ◽  
Calcium Sensing ◽  
Standard Procedures ◽  
Renal Complication ◽  
Serum Pth ◽  
Bone Complications

Context: Primary hyperparathyroidism (PHPT) shows a great variability in clinical course and severity. Data concerning the association between polymorphic variants of the gene encoding the calcium-sensing receptor (CaSR) and clinical characteristics of PHPT are not conclusive. Objective: To evaluate the frequency of three polymorphisms; A986S, R990G, and Q1011E of CaSR in patients with PHPT and to correlate the genotypes with clinical and biochemical parameters. Patients and methods: The study included 94 consecutive unrelated patients referred to our Departments for PHPT diagnosis and management between 2000 and 2005 and 137 age and sex-matched healthy subjects. Patients and controls were genotyped according to standard procedures. Due to the rarity of 990G allele, homozygous and heterozygous subjects were grouped in R/G+G/G set. All PHPT patients were studied for calcium metabolism parameters and renal and bone complications. Results: The proportion of CaSRvariants was similar in PHPT patients and controls. In PHPT patients, only R990G polymorphism was associated with disease parameters; in comparison with R/R, R/G+G/G patients showed lower mean serum parathyroid hormone (PTH) and phosphate levels (139.9 ± 62.2 vs 199.9 ± 136.3 pg/ml, P < 0.05 and 0.69 ± 0.12 vs 0.81 ± 0.18 mmol/l, P = 0.031 respectively), higher mean 24-h urine calcium concentration and calcium excretion (9.05 ± 2.05 vs 6.77 ± 4.31 mmol/24 h, P = 0.012 and 67 ± 20 vs 51 ± 26 μmol/l GF, P = 0.039), and increased prevalence of nephrolithiasis (90.0 vs 44.2%, P = 0.007). Conclusions: The study showed that patients with PHPT, bearing the 990G allele, had lower serum PTH levels and higher urinary calcium excretion in comparison with the other genotype, suggesting an increased sensitivityof the variant receptor to extracellular calcium. Since this variant was associated with increased occurrence of nephrolithiasis, analysis of this polymorphism might help to predict renal complication of the disease.

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