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

Han, Guiyan; Wang, Ou; Nie, Min; Zhu, Yan; Meng, Xunwu; Hu, Yingying; Liu, Huaicheng; Xing, Xiaoping

doi:10.1530/eje-13-0441

Cited by 18 publications

(10 citation statements)

References 37 publications

(47 reference statements)

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“…For the associations between CaSR polymorphisms and urinary calcium concentration, ten papers [ 5 , 13 – 15 , 18 – 23 ] were retrieved according to the inclusion criteria. The process of study selection is also shown in Figure 1 .…”

Section: Resultsmentioning

confidence: 99%

The G Allele of CaSR R990G Polymorphism Increases Susceptibility to Urolithiasis and Hypercalciuria: Evidences from a Comprehensive Meta-Analysis

Liu

Wang

et al. 2015

BioMed Research International

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Background. The calcium-sensing receptor gene (CaSR) is a candidate to explain urolithiasis. A number of case-control studies were conducted to investigate associations between CaSR polymorphisms with risks of hypercalciuria and urolithiasis in humans. But the results were still inconsistent. Methods. A meta-analysis was performed to address this issue. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of associations between CaSR polymorphisms and the risk of urolithiasis. The pooled standardized mean difference (SMD) with 95% CI was used for the meta-analysis of CaSR polymorphisms and urine calcium concentration. Results. For urolithiasis association, the SS genotype of A986S polymorphism was a risk factor for urolithiasis in Asians and PHPT patients, but a protective factor in Caucasians. The GG genotype of R990 polymorphism was associated with an increased risk of urolithiasis, especially in Caucasians and healthy population. Regarding urine calcium concentration association, individuals with the G allele had a higher level of urine calcium than the noncarriers. Conclusions. This meta-analysis revealed that the G allele of CaSR R990G polymorphism increases susceptibility to urolithiasis and hypercalciuria. The A986S and Q1011E polymorphisms were associated with urolithiasis and hypercalciuria in specific populations.

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Section: Resultsmentioning

confidence: 99%

The G Allele of CaSR R990G Polymorphism Increases Susceptibility to Urolithiasis and Hypercalciuria: Evidences from a Comprehensive Meta-Analysis

Liu

Wang

et al. 2015

BioMed Research International

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“…However, a dozen cases of parathyroid adenomas associated with CASR mutations have been reported, with two families having adenoma and/or familial hyperplasia of the parathyroids with papillary microcarcinoma [7–14]. Moreover, the R990G variant of CaSR seems to be more common in the general Chinese population, but also in Chinese patients with hyperparathyroidism [15]. The coexistence of hyperparathyroidism and hypocalciuric hypercalcaemia syndrome was also identified in 4 out of 139 patients from a hyperparathyroid Caucasian population [16].…”

Section: Genetic Causesmentioning

confidence: 99%

Diseases associated with calcium-sensing receptor

Vahé

Benomar

Espiard

et al. 2017

Orphanet J Rare Dis

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The calcium-sensing receptor (CaSR) plays a pivotal role in systemic calcium metabolism by regulating parathyroid hormone secretion and urinary calcium excretion. The diseases caused by an abnormality of the CaSR are genetically determined or are more rarely acquired. The genetic diseases consist of hyper- or hypocalcemia disorders. Hypercalcaemia disorders are related to inactivating mutations of the CASR gene either heterozygous (autosomal dominant familial benign hypercalcaemia, still named hypocalciuric hypercalcaemia syndrome type 1) or homozygous (severe neonatal hyperparathyroidism). The A986S, R990G and Q1011E variants of the CASR gene are associated with higher serum calcium levels than in the general population, hypercalciuria being also associated with the R990G variant. The differential diagnosis consists in the hypocalciuric hypercalcaemia syndrome, types 2 (involving GNA11 gene) and 3 (involving AP2S1 gene); hyperparathyroidism; abnormalities of vitamin D metabolism, involving CYP24A1 and SLC34A1 genes; and reduced GFR. Hypocalcemia disorders, which are more rare, are related to heterozygous activating mutations of the CASR gene (type 1), consisting of autosomal dominant hypocalcemia disorders, sometimes with a presentation of pseudo-Bartter’s syndrome. The differential diagnosis consists of the hypercalciuric hypocalcaemia syndrome type 2, involving GNA11 gene and other hypoparathyroidism aetiologies. The acquired diseases are related to the presence of anti-CaSR antibodies, which can cause hyper- or especially hypocalcemia disorders (for instance in APECED syndromes), determined by their functionality. Finally, the role of CaSR in digestive, respiratory, cardiovascular and neoplastic diseases is gradually coming to light, providing new therapeutic possibilities. Two types of CaSR modulators are known: CaSR agonists (or activators, still named calcimimetics) and calcilytic antagonists (or inhibitors of the CasR). CaSR agonists, such as cinacalcet, are indicated in secondary and primary hyperparathyroidism. Calcilytics have no efficacy in osteoporosis, but could be useful in the treatment of hypercalciuric hypocalcaemia syndromes.

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“…Of those, four papers [26][27][28][29] showed that R990G gene polymorphism was associated with the risk of urolithiasis with variable odd ratio, ranging from 1.24 to 8.07 (G vs. R). On the other hand, four other studies [30][31][32][33] failed to confirm the correlation. Our pooled calculation revealed that R allele and RR genotype were associated with decreased risk of urolithiasis.…”

Section: Discussionmentioning

confidence: 82%

Association between calcium-sensing receptor (CaSR) R990G, CaSR A986S, and CaSR Q1011E gene polymorphisms and the risk of urolithiasis: a meta-analysis

Daryanto

Purnomo

Gunawan

et al. 2019

Egypt J Med Hum Genet

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Backgrounds: In the last two decades, studies have been widely carried out to assess the association between singlenucleotide polymorphisms (SNPs) of calcium-sensing receptor (CaSR) gene in exon 7 and the risk of urolithiasis. However, inconsistency across the studies was reported. Therefore, our current study aimed to perform a meta-analysis concerning the association between the risk of urolithiasis and the gene polymorphisms of CaSR R990G, CaSR A986S, and CaSR Q1011E. Methods: Published papers from PubMed, Embase, Cohcrane, and Web of science were included for the study, and they were analyzed using fixed or random effect model. Results: A total of 11 papers consisting of eight papers evaluating CaSR R990G, nine papers evaluating CaSR A986S, and five papers evaluating CaSR Q1011E were included in our analysis. Our pooled calculation found that protective effect against urolithiasis was observed in R allele and RR genotype of CaSR R990G and A allele and AA genotype of CaSR A986S. Conversely, increased susceptibility to urolithiasis was found in G allele and RG genotype of CaSR R990G and S allele of CaSR A986S. Interestingly, our findings in subgroup analysis confirmed that the correlation between CaSR R990G and urolithiasis was found in Caucasian population. Meanwhile, in Asian population, the association was observed in CaSR A986S. Conclusions: CaSR R990G and CaSR A986S, but not CaSR Q1011E, are associated with the risk of urolithiasis.

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

Cited by 18 publications

References 37 publications

The G Allele of CaSR R990G Polymorphism Increases Susceptibility to Urolithiasis and Hypercalciuria: Evidences from a Comprehensive Meta-Analysis

The G Allele of CaSR R990G Polymorphism Increases Susceptibility to Urolithiasis and Hypercalciuria: Evidences from a Comprehensive Meta-Analysis

Diseases associated with calcium-sensing receptor

Association between calcium-sensing receptor (CaSR) R990G, CaSR A986S, and CaSR Q1011E gene polymorphisms and the risk of urolithiasis: a meta-analysis

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