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

Scillitani, Alfredo; Guarnieri, Vito; Battista, Claudia; Geronimo, Simona De; Muscarella, Lucia Anna; Chiodini, Iacopo; Cignarelli, Mauro; Minisola, Salvatore; Bertoldo, Francesco; Francucci, C M; Malavolta, N; Piovesan, Alessandro; Mascia, Maria Lucia; Muscarella, Silvana; Hendy, Geoffrey N.; D’Agruma, Leonardo; Cole, David E. C.

doi:10.1210/jc.2006-0857

Cited by 85 publications

(72 citation statements)

References 36 publications

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“…Therefore, common variants of the CASR gene modulate the effect of PTH-related hypercalcaemia on renal calcium handling ( Table 4). The 990G allele, located in the cytoplasmic tail of the receptor protein, has been associated with increased renal calcium excretion in PHPT Italian patients (78,79). Two further single nucleotide polymorphisms (SNPs), located in the regulatory region of the CASR gene, rs7652589 and rs1501899, are associated with kidney stones occurrence in PHPT patients (80).…”

Section: Calcium-sensing Receptor (Casr)mentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects

Verdelli

Corbetta

2017

European Journal of Endocrinology

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Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. Kidney is a target of both chronic elevated PTH and calcium in PHPT. The classic PHPT complications of symptomatic kidney stones and nephrocalcinosis have become rare and the PHPT current presentation is asymptomatic with uncertain and long-lasting progression. Nonetheless, the routine use of imaging and of biochemical determinations have revealed the frequent occurrence of asymptomatic kidney stones, hypercalciuria and reduced kidney function in asymptomatic PHPT patients. Though the pathogenesis is far from being elucidated, PHPT is associated with reduced renal function, in terms of estimated glomerular filtration rate, and related increased morbidity and mortality. In the last decade, the effort of the Kidney Disease: Improving Global Outcomes (KDIGO) panel of experts highlighted that even mild reduction of kidney function is associated with increased risk of cardiovascular disease. These considerations provided the basis for the Fourth Workshop recommendations of a more extensive diagnostic workout about kidney features and of wider criteria for parathyroid surgery including asymptomatic kidney disease. Moreover, kidney involvement in PHPT is likely to be affected by variants of genes coding the key molecules regulating the calcium and ions renal handling; these features might have clinical relevance and should be considered both during diagnostic workout and follow-up. Finally, the effects of parathyroid surgery and of medical treatment on kidney involvement of PHPT are reviewed.

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Section: Calcium-sensing Receptor (Casr)mentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects

Verdelli

Corbetta

2017

European Journal of Endocrinology

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“…The frequency of the AR/AR haplotype was higher in this Chinese population, although the difference was not significant. By contrast, Scillitani et al (3) found that there was a lower frequency of the AR haplotype in Italian PHPT patients than in controls (66.7 vs 71.9%). The results suggest that the resulting amino acid changes might decrease the inhibitory activity of the mutated receptor.…”

Section: Discussionmentioning

confidence: 85%

“…Interestingly, the clinical manifestation and severity of PHPT vary markedly. The variation in PHPT presentation has been reported to be associated with genetic variation of the vitamin D receptor, estrogen receptor, PTH, and calcium-sensing receptor (CASR) (1,2,3).…”

Section: Introductionmentioning

confidence: 99%

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

Han

Wang

Nie

et al. 2013

European Journal of Endocrinology

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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: 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. Results: 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 ratioZ1.134, 95% CI: 1.008, 1.277, and PZ0.036). 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 K2.20 (K2.63, K0.32) in patients with the GG genotype, and it was significantly lower in patients with the RRCRG genotype (K2.53 (K3.70, K1.72) PZ0.036). 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; PZ0.025). The prevalence of osteoporosis and parathyroid carcinomas was higher in Chinese PHPT patients with the R allele. Conclusion: 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.

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“…Moreover, male gender and a young age at the time of diagnosis of primary hyperparathyroidism provide additional risks for the development of renal stones (8). Although hypercalciuria (9), increased plasma 1,25-dihydroxyvitamin D levels (10) and polymorphism in the calcium-sensing receptor (11) have been proposed as causes of the development of nephrolithiasis, the precise relationship between primary hyperparathyroidism and nephrolithiasis remains unclear (8). Computed tomography is the radiographic test of choice for diagnosis, with parenchymal calcifications being pathognomonic.…”

Section: Discussionmentioning

confidence: 99%

Nontyphoidal Salmonella Urinary Tract Infection in a Case of Hyperparathyroidism and Nephrocalcinosis

Shi

et al. 2013

West Indian Med J

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Nontyphoidal Salmonella infections often present with self-limited gastroenteritis. Extraintestinal focal infections are uncommon but have high mortality and morbidity. Urinary tract infection caused by nontyphoidal RESUMEN Las infecciones por Salmonella no tifoidea se presentan a menudo con gastroenteritis auto-limitada. Las infecciones extra-intestinales focales son poco frecuentes, pero tienen una alta mortalidad y morbilidad. La infección de las vías urinarias causada por la

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

Abstract: 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.

Cited by 85 publications

References 36 publications

MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects

MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects

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

Nontyphoidal Salmonella Urinary Tract Infection in a Case of Hyperparathyroidism and Nephrocalcinosis

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