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Risk of nephrolithiasis in primary hyperparathyroidism is associated with two polymorphisms of the calcium-sensing receptor gene
Risk of nephrolithiasis in primary hyperparathyroidism is associated with two polymorphisms of the calcium-sensing receptor gene
- Source :
- Journal of nephrology. 28(1)
- Publication Year :
- 2014
-
Abstract
- Aims: Two single-nucleotide polymorphisms (SNPs) at the calcium-sensing receptor (CASR) gene were previously associated with kidney stones in patients with primary hyperparathyroidism (PHPT): rs1501899, likely associated with a decrease in CASR expression, and Arg990Gly, causing a gain of CASR function. To evaluate the interaction of these two SNPs in the stone risk, we tested the association of stones with the genotype at both SNPs in PHPT patients and the association of rs1501899 with CASR expression as messenger RNA (mRNA) in human kidney samples.Methods and results: Two hundred and ninety-six PHPT patients were genotyped at the rs1501899 and Arg990Gly SNPs. Minor allele frequency at tested SNPs was higher in PHPT stone formers relative to non-stone forming patients. PHPT patients carrying one or two copies of the minor allele at both rs1501899 and Arg990Gly (n=16) had the maximal risk of stones (odds ratio, OR 8.3) and higher serum ionized calcium compared with homozygous patients for the wild-type allele at both SNPs. CASR expression as mRNA was measured by real time polymerase chain reaction (PCR) in normal kidney medulla samples from 109 subjects. CASR mRNA was significantly lower in medulla samples from homozygotes for the minor allele at rs1501899 than in subjects with other genotypes.Conclusions: We conclude that the simultaneous presence of the minor allele at rs1501899 and Arg990Gly may amplify the kidney stone risk in PHPT patients, despite their apparently opposite effects on CASR function in the kidney.
- Subjects :
- Nephrology
Male
medicine.medical_specialty
endocrine system diseases
Genotype
Single-nucleotide polymorphism
Nephrolithiasis
Polymorphism, Single Nucleotide
Risk Factors
Internal medicine
Calcium-sensing receptor
Nephrolithiasi
medicine
Humans
RNA, Messenger
Allele
Kidney stone
Alleles
Hyperparathyroidism
Kidney Medulla
business.industry
Risk Factor
Homozygote
Middle Aged
medicine.disease
Hyperparathyroidism, Primary
Endocrinology
Kidney stones
Calcium
Female
business
Receptors, Calcium-Sensing
Primary hyperparathyroidism
Human
Subjects
Details
- ISSN :
- 17246059
- Volume :
- 28
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of nephrology
- Accession number :
- edsair.doi.dedup.....ae4611744373d156fe08e4ad494437b3