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

2018 ◽  
Vol 11 (2) ◽  
pp. 417 ◽  
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.

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.

Biased calcium-sensing receptor signalling in the pathogenesis of kidney stone disease

2021 ◽  
Vol 79 ◽  
pp. S329
Author(s):  
M. Goldsworthy ◽  
A. Wiberg ◽  
B.W. Turney ◽  
D. Furniss ◽  
R.V. Thakker ◽  
...  
Keyword(s):  
Kidney Stone ◽  
Stone Disease ◽  
Calcium Sensing Receptor ◽  
Kidney Stone Disease ◽  
Receptor Signalling ◽  
Calcium Sensing

scholarly journals Genotyping of Essential Hypertension Single-Nucleotide Polymorphisms by a Homogeneous PCR Method with Universal Energy Transfer Primers

2002 ◽  
Vol 48 (12) ◽  
pp. 2131-2140 ◽  
Author(s):  
Chikh Bengra ◽  
Theodore E Mifflin ◽  
Yuri Khripin ◽  
Paolo Manunta ◽  
Scott M Williams ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Single Nucleotide Polymorphisms ◽  
Restriction Endonucleases ◽  
Control Group ◽  
Italian Population ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Hypertensive Patients ◽  
Unique Restriction ◽  
Set Up

Abstract Background: Human hypertension is a complex, multifactorial disease with a heritability of more than 30–50%. A genetic screening test based on analysis of multiple single-nucleotide polymorphisms (SNPs) to assess the likelihood of developing hypertension would be helpful for disease management. Methods: Tailed allele-specific primers were designed to amplify by PCR six biallelic SNP loci [three in G protein-coupled receptor kinase type 4 (GRK4): R65L, A142V, and A486V; two in angiotensinogen: −6G→A and M235T; and one in aldosterone synthase: −344C→T] associated with essential hypertension. PCRs of SNP loci were coupled (via a common sequence of 21 nucleotide tails) to incorporate Universal Amplifluor™ primers labeled with fluorescein or sulforhodamine in a homogeneous format. Use of Amplifluors in SNP PCRs produced labeled amplicons, the fluorescence of which was quantified by a microplate reader and then analyzed via an Excel macro to provide genotypes for all six SNP loci. Unique restriction endonucleases were identified for five SNP loci that could independently confirm homogeneous PCR results when needed. Results: We developed six homogeneous PCR assays that were set up, performed, and fluorometrically analyzed in 96-well microplates. Allele frequencies were determined for six SNPs in 60 Italian hypertensive patients and a control group of 60 normotensive persons. A significant correlation (P = 0.034) between one SNP [GRK4 (A486V)] and the hypertensive patients was observed. Genotyping results for five of six SNPs were confirmed by digesting corresponding amplicons with locus-specific restriction endonucleases. Conclusions: We developed a simple and homogeneous fluorescent protocol that has been used to determine the SNP genotype for six loci in a population of hypertensive and normotensive persons. We also observed a significant association (P = 0.034) between one SNP (A486V) and an Italian population of mildly hypertensive patients.

scholarly journals Association of single-nucleotide polymorphisms in the ESR2 and FSHR genes with poor ovarian response in infertile Jordanian women

2021 ◽  
Vol 48 (1) ◽  
pp. 69-79
Author(s):  
Amer Mahmoud Sindiani ◽  
Osamah Batiha ◽  
Esra’a Al-zoubi ◽  
Sara Khadrawi ◽  
Ghadeer Alsoukhni ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Statistical Significance ◽  
Ovarian Response ◽  
Control Group ◽  
P Value ◽  
Case Group ◽  
Nucleotide Polymorphisms ◽  
Poor Ovarian Response ◽  
Single Nucleotide ◽  
Number Of Patients

Objective: Poor ovarian response (POR) refers to a subnormal follicular response that leads to a decrease in the quality and quantity of the eggs retrieved after ovarian stimulation during assisted reproductive treatment (ART). The present study investigated the associations of multiple variants of the estrogen receptor 2 (ESR2) and follicle-stimulating hormone receptor (FSHR) genes with POR in infertile Jordanian women undergoing ART.Methods: Four polymorphisms, namely ESR2 rs1256049, ESR2 rs4986938, FSHR rs6165, and FSHR rs6166, were investigated in 60 infertile Jordanian women undergoing ART (the case group) and 60 age-matched fertile women (the control group), with a mean age of 33.60±6.34 years. Single-nucleotide polymorphisms (SNPs) were detected by restriction fragment length polymorphism and then validated using Sanger sequencing.Results: The p-value of the difference between the case and control groups regarding FSHR rs6166 was very close to 0.05 (p=0.054). However, no significant differences were observed between the two groups in terms of the other three SNPs, namely ESR2 rs1256049, ESR2 rs4986938, and FSHR rs6165 (p=0.561, p=0.433, and p=0.696, respectively).Conclusion: The association between FSHR rs6166 and POR was not statistically meaningful in the present study, but the near-significant result of this experiment suggests that statistical significance might be found in a future study with a larger number of patients.

scholarly journals Association Analysis of Single Nucleotide Polymorphisms in the 5′ Regulatory Region of the IL-6 Gene with Eimeria tenella Resistance in Jinghai Yellow Chickens

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 890 ◽  
Author(s):  
Hailiang Yu ◽  
Wenbin Zou ◽  
Shijie Xin ◽  
Xiaohui Wang ◽  
Changhao Mi ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Association Analysis ◽  
Direct Sequencing ◽  
Regulatory Region ◽  
Eimeria Tenella ◽  
Least Square ◽  
Bursa Of Fabricius ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Interleukin 6 (IL-6) is an immunoregulatory cytokine involved in various inflammatory and immune responses. To investigate the effects of single nucleotide polymorphisms (SNPs) and haplotypes of IL-6 on resistance to Eimeria tenella (E. tenella), SNPs in the 5′ regulatory region of IL-6 were detected with direct sequencing, and the effects of SNPs and haplotypes on resistance to E. tenella were analyzed by the least square model in Jinghai yellow chickens. Nineteen SNPs were identified in the 5′ regulation region of IL-6, among which three SNPs were newly discovered. The SNP association analysis results showed that nine of the SNPs were significantly associated with E. tenella resistance indexes; the A-483G locus was significantly associated with the GSH-Px, IL-2, and IL-17 indexes (p < 0.05); the C-447G locus was significantly associated with the SOD, GSH-Px, IL-17, and IL-2 indexes (p < 0.05); and the G-357A locus had significant effects on the CAT and IL-16 indexes (p < 0.05). Haplotype analysis showed that H2H3 and H2H5 were favorable haplotype combinations with good coccidium resistance. Furthermore, we used qRT-PCR and observed that the expression of IL-6 in the infection group was higher than that in the control group in the liver, proventriculus, small intestine, thymus, kidney, and bursa of Fabricius and extremely significantly different than that in the cecum especially (p < 0.01). In summary, SNPs and haplotypes in the 5′ regulatory region of IL-6 have important effects on E. tenella resistance, and the results will provide a reference for molecular marker selection of E. tenella resistance in Jinghai yellow chickens.

Genetic association study of SOX2 gene polymorphisms with high myopia in a Chinese population

2020 ◽  
pp. 112067212090466
Author(s):  
Lan Li ◽  
Ying Juan Cui ◽  
Yunchun Zou ◽  
Liyuan Yang ◽  
Ximin Yin ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Chinese Population ◽  
High Myopia ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Spherical Equivalent ◽  
Chi Square ◽  
Single Nucleotide ◽  
Sox2 Gene ◽  
Chi Square Test

Purpose: The aim of this study is to investigate whether SOX2 gene variants were associated with high myopia in a Chinese population. Methods: This study is conducted using case-control association analysis. This study recruited 83 healthy controls (with binocular spherical equivalent between –0.50 and +0.50 D) and 117 high myopia cases (spherical equivalent > –6.00 D in both eyes). Three single-nucleotide polymorphisms were selected from HapMap database for genotyping by direct sequencing. Statistical software (SPSS 22.0) was used for statistical analysis. The chi-square test was used to examine the difference in the frequency between cases and controls. Results: Genotype distributions in the three single-nucleotide polymorphisms were all in accordance with the Hardy–Weinberg equilibrium. The differences of rs4575941 locus genotype frequency and allele frequency between the case group and the control group were statistically significant (p = .043 and p = .029, respectively). The rs4575941 allele G frequency in the high myopia group was significantly higher than that in the control group with an odds ratio value of 1.579. However, the value of a chi-square test for the trend was 0.029, and after Bonferroni test, the p value was .087. Conclusion: In Chinese population, rs4575941 in SOX2 gene was likely to play some roles in the genetic susceptibility to high myopia; the rs4575941 allele G might be a risk gene for high myopia.

scholarly journals Correlation between miRNA target site polymorphisms in the 3′ UTR of AVPR1A and the risk of hypertension in the Chinese Han population

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Liuping Zhang ◽  
Jinwei Liu ◽  
Peng Cheng ◽  
Fangchao Lv
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Mirna Target ◽  
Direct Sequencing ◽  
Chinese Han Population ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Single Nucleotide ◽  
Han Population ◽  
Increased Risk

Abstract We aimed to study the relationship between rs11174811 and rs3803107 single nucleotide polymorphisms (SNPs) in miRNA target sites of the 3′ UTR in the arginine vasopressin receptor 1a gene (AVPR1A) and the risk of hypertension in the Chinese Han population. The genotypes at rs11174811 and rs3803107 were analyzed by direct sequencing in 425 Chinese Han patients with hypertension and 425 healthy subjects. AVPR1A expression was investigated by transfecting miR-526b, miR-375, and miR-186 mimics into human umbilical vein endothelial cells (HUVECs) containing AVPR1A rs11174811 CC, CA/AA and AVPR1A rs3803107 GG, GA/AA genotypes. The A alleles of rs11174811 (adjusted OR = 1.424, 95% CI: 1.231–1.599, P<0.001) and rs3803107 (adjusted OR = 1.222, 95% CI: 1.092–1.355; P=0.001) were high risk factors for hypertension. Plasma levels of miR-526b, miR-375, and miR-186 were higher in the study group than in the control group (P<0.001). The expression levels of AVPR1A mRNA in AVPR1A rs11174811 and rs3803107 mutant HUVECs were higher than those in wild-type cells (t = 8.811, 4.068 and P=0.001, 0.015, respectively). The single nucleotide polymorphisms rs11174811 and rs3803107 in the AVPR1A gene are associated with an increased risk of hypertension in the Chinese Han population. This may be related to the effect of these variants on the regulation of AVPR1A expression by miRNAs.

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