Associations between single nucleotide polymorphisms in the calcium sensing receptor and chronic kidney disease-mineral and bone disorder in cats

Abstract Purpose Observational studies have associated obesity with chronic kidney disease (CKD) and arterial stiffness, but the causality remains unclear. We aimed to investigate the causality of obesity with CKD and arterial stiffness using Mendelian randomization (MR) analysis. Methods We genotyped 14 body mass index (BMI)-associated variants validated in East Asians in 11384 Chinese adults. A genetic risk score based on the 14 variants and the 14 individual single nucleotide polymorphisms were respectively used as instrumental variables (IVs). CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m 2. Arterial stiffness was defined as brachial-ankle pulse wave velocity >1550 cm/s. Results Using the genetic risk score as the IV, we demonstrated causal relations of each 1-standard deviation increment in BMI with CKD (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.11-5.00) and arterial stiffness (OR: 1.71; 95% CI: 1.22-2.39). Using the 14 single nucleotide polymorphisms individually as IVs, each 1-standard deviation increment in BMI casually associated with CKD (OR: 2.58; 95% CI: 1.39-4.79) and arterial stiffness (OR: 1.87; 95% CI: 1.24-2.81) in the inverse-variance weighted analysis, and MR-Egger regression revealed no evidence of horizontal pleiotropy (Both P for intercept≥0.34). The causality between obesity and CKD was validated in two-sample MR analysis among Europeans (681275 of Genetic Investigation of ANthropometric Traits and 133413 of CKD Genetics). Conclusions This study provided novel insights into causality of obesity with CKD and arterial stiffness, highlighting the importance of weight management for primary prevention and control of subclinical vascular diseases.

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SINGLE-NUCLEOTIDE POLYMORPHISMS OF CALCIUM-SENSING RECEPTOR ENCODING GENE ASSOCIATED WITH CALCIUM KIDNEY STONE DISEASE IN BABYLON PROVINCE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i2.22064 ◽

2018 ◽

Vol 11 (2) ◽

pp. 417 ◽

Cited By ~ 1

Author(s):

Zahraa Isam ◽

Rabab Omran ◽

Ammad Hassan Mahmood

Keyword(s):

Amino Acid ◽

Single Nucleotide Polymorphisms ◽

Kidney Stone ◽

Stone Disease ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Calcium Sensing Receptor ◽

Single Nucleotide ◽

Kidney Stone Disease ◽

Calcium Sensing

Objective: The calcium-sensing receptor (CASR) is a G-protein-coupled receptor that is mainly expressed in the parathyroid and the kidneys where it regulates parathyroid hormone secretion and renal tubular calcium reabsorption. Inactivating and activating CASR gene due to mutations severally caused hypercalcemia or hypocalcemia disorders. The aim of the study was to investigate the risk factor of CASR rs1801725 (Ala986Ser) patients with renal disease.Method: The blood samples were collected from 100 patients and divided into two groups, each one containing 50 samples; chronic kidney disease and end-stage renal disease, who admitted Merjan Teaching Hospital in Babylon Province, Iraq, from February to July 2016. In addition, healthy persons as a control group (50 samples). Genotyping of CASR single-nucleotide polymorphisms (SNP) was performed using a polymerase chain reaction technique, followed by single-strand conformation polymorphism. Accordingly, these DNA polymorphisms were confirmed using DNA sequencing.Results: The conformational haplotypes of CASR, exon7 NCBI Primer3plus reference were obtained in three patterns, including two, three, and four bands, due to the presence SNPs within the studied region. These SNPs leads to change three amino acid residues of CASR, including amino acid substitutions were Ala 128→ Ser 128, Leu 155→Tye 155, and Leu 156→ Ser 156 that may affect or modified the tertiary structure of the receptor, subsequently the function like the affinity to calcium ion may be effected.Conclusion: These results suggest that the variants of CASR SNP, namely, rs1801725 might be involved in susceptibility to kidney stone disease.

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Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA is associated with the kidney survival time in chronic kidney disease patients

Renal Failure ◽

10.3109/0886022x.2014.976132 ◽

2014 ◽

Vol 37 (1) ◽

pp. 108-112 ◽

Cited By ~ 3

Author(s):

Jinsheng Xu ◽

Zhanjun Guo ◽

Yaling Bai ◽

Junxia Zhang ◽

Liwen Cui ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Mitochondrial Dna ◽

Kidney Disease ◽

Single Nucleotide Polymorphisms ◽

Survival Time ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Loop Region ◽

D Loop

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Influence of Single-Nucleotide Polymorphisms on C-Reactive Protein Levels in Chronic Kidney Disease Before and After Kidney Transplantation

Transplantation Proceedings ◽

10.1016/j.transproceed.2008.04.021 ◽

2008 ◽

Vol 40 (10) ◽

pp. 3349-3353

Author(s):

A.C. Cordeiro ◽

I. de Castro ◽

R. Pecoits-Filho ◽

R. Ramasawmy ◽

H. Rodrigues ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Transplantation ◽

Kidney Disease ◽

Single Nucleotide Polymorphisms ◽

Nucleotide Polymorphisms ◽

C Reactive Protein ◽

Single Nucleotide ◽

Protein Levels ◽

Reactive Protein ◽

Before And After

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-0857 ◽

2007 ◽

Vol 92 (1) ◽

pp. 277-283 ◽

Cited By ~ 49

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.

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