scholarly journals Influence of Genetic Variation in COMT on Cisplatin-Induced Nephrotoxicity in Cancer Patients

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 358
Author(s):  
Bram C. Agema ◽  
Stijn L.W. Koolen ◽  
Mirjam de With ◽  
Nadia van Doorn ◽  
Niels Heersche ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Odds Ratio ◽  
Chemotherapeutic Agent ◽  
Kidney Injury ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Number Of Patients ◽  
Low Incidence ◽  
Grade 3

Cisplatin is a chemotherapeutic agent widely used for multiple indications. Unfortunately, in a substantial set of patients treated with cisplatin, dose-limiting acute kidney injury (AKI) occurs. Here, we assessed the association of 3 catechol-O-methyltransferase (COMT) single nucleotide polymorphisms (SNPs) with increased cisplatin-induced nephrotoxicity. In total, 551 patients were genotyped for the 1947 G>A (Val158Met, rs4680), c.615 + 310 C>T (rs4646316), and c.616–367 C>T (rs9332377) polymorphisms. Associations between these variants and AKI grade ≥3 were studied. The presence of a homozygous variant of c.616-367C>T was associated with a decreased occurrence of AKI grade 3 toxicity (p = 0.014, odds ratio (OR) 0.201, 95% confidence interval (CI) (0.047–0.861)). However, we could not exclude the role of dehydration as a potential cause of AKI in 25 of the 27 patients with AKI grade 3, which potentially affected the results substantially. As a result of the low incidence of AKI grade 3 in this dataset, the lack of patients with a COMT variant, and the high number of patients with dehydration, the association between COMT variants and AKI does not seem clinically relevant.

scholarly journals Genetic Association Study of KCNQ5 Polymorphisms with High Myopia

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Xuan Liao ◽  
Maurice K. H. Yap ◽  
Kim Hung Leung ◽  
Patrick Y. P. Kao ◽  
Long Qian Liu ◽  
...  
Keyword(s):  
Refractive Error ◽  
Odds Ratio ◽  
High Myopia ◽  
Permutation Test ◽  
Minor Allele ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Association Testing ◽  
Hypersensitive Sites

Identification of genetic variations related to high myopia may advance our knowledge of the etiopathogenesis of refractive error. This study investigated the role of potassium channel gene (KCNQ5) polymorphisms in high myopia. We performed a case-control study of 1563 unrelated Han Chinese subjects (809 cases of high myopia and 754 emmetropic controls). Five tag single-nucleotide polymorphisms (SNPs) of KCNQ5 were genotyped, and association testing with high myopia was conducted using logistic regression analysis adjusted for sex and age to give Pasym values, and multiple comparisons were corrected by permutation test to give Pemp values. All five noncoding SNPs were associated with high myopia. The SNP rs7744813, previously shown to be associated with refractive error and myopia in two GWAS, showed an odds ratio of 0.75 (95% CI 0.63–0.90; Pemp = 0.0058) for the minor allele. The top SNP rs9342979 showed an odds ratio of 0.75 (95% CI 0.64–0.89; Pemp = 0.0045) for the minor allele. Both SNPs are located within enhancer histone marks and DNase-hypersensitive sites. Our data support the involvement of KCNQ5 gene polymorphisms in the genetic susceptibility to high myopia and further exploration of KCNQ5 as a risk factor for high myopia.

scholarly journals MassArray analysis of genomic susceptibility variants in ovarian cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sonali Verma ◽  
Indu Sharma ◽  
Varun Sharma ◽  
Amrita Bhat ◽  
Ruchi Shah ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Odds Ratio ◽  
Gene Interaction ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Jammu And Kashmir ◽  
Interactive Analysis ◽  
Strong Existence

AbstractOvarian cancer (OC), a multifaceted and genetically heterogeneous malignancy is one of the most common cancers among women. The aim of the study is to unravel the genetic factors associated with OC and the extent of genetic heterogeneity in the populations of Jammu and Kashmir (J&K).Using the high throughput Agena MassARRAY platform, present case control study was designed which comprises 200 histopathological confirmed OC patients and 400 age and ethnicity matched healthy controls to ascertain the association of previously reported eleven single nucleotide polymorphisms (SNPs) spread over ten genes (DNMT3A, PIK3CA, FGFR2, GSTP1, ERCC5, AKT1, CASC16, CYP19A1, BCL2 and ERCC1) within the OC population of Jammu and Kashmir, India. The association of each variant was estimated using logistic regression analyses. Out of the 11 SNPs the odds ratio observed for three SNPs; rs2699887 was (1.72 at 95% CI: 1.19–2.48, p = 0.004), rs1695 was (1.87 at 95% CI: 1.28–2.71, p = 0.001), and rs2298881 was (0.66 at 95% CI: 0.46–0.96, p = 0.03) were found significantly associated with the OC after correction with confounding factors i.e. age & BMI. Furthermore, the estimation of interactive analyses was performed and odds ratio observed was 2.44 (1.72–3.47), p value < 0. 001 suggests that there was a strong existence of interplay between the selected genetic variants in OC, which demonstrate that interactive analysis highlights the role of gene–gene interaction that provides an insight among multiple little effects of various polymorphisms in OC.

scholarly journals Association between Kidney Injury Molecule-1 Gene Polymorphism and Acute Kidney Injury in Lebanese population

2019 ◽  
Vol 3 (3) ◽  
pp. 9
Author(s):  
Hajar Karaali ◽  
Jamilah Borjac
Keyword(s):  
Acute Kidney Injury ◽  
Single Nucleotide Polymorphisms ◽  
Gene Polymorphism ◽  
Kidney Injury ◽  
Injury Incidence ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Lebanese Population ◽  
Exon 4 ◽  
Kidney Injury Molecule 1

Background: Acute kidney injury is a common condition associated with longer hospital stay and increased mortality. Kidney injury molecule-1 is one of the early and sensitive biomarkers for acute kidney injury diagnosis. Therefore we examined the relationship between kidney injury molecule-1 gene polymorphism and acute kidney injury in Lebanese hospitalized patients. Methods: Genomic DNA was isolated from blood samples collected from 50 patients and 40 controls. Kidney injury molecule-1 exon 4 was amplified by polymerase chain reaction. The amplified products were sequenced. Serum creatinine and urea levels were measured. Results: Three out of the five known single nucleotide polymorphisms showed significant association with susceptibility to the disease (P ≤ 0.05). Data analysis implied that carriers of the risk allele of these 3 single nucleotide polymorphisms were more predisposed to acute kidney injury. No association was found between the studied nucleotides variations and creatinine/urea levels. Haplotype analysis showed high association of the block CTA with acute kidney injury incidence and high creatinine and urea levels. Conclusions: Our results suggest that polymorphisms in exon 4 of kidney injury molecule-1 in the Lebanese population may be associated with acute kidney injury.

Single nucleotide polymorphisms analysis of BRAC and ERCC1 as predictor of recurrence after chemoradiation for cervical cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13540-e13540
Author(s):  
Luis Roberto Féliz ◽  
Verónica Pereira ◽  
Mariano Monzo ◽  
Carmen Munoz ◽  
Pere Fuste ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Locally Advanced ◽  
Initial Response ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Number Of Patients ◽  
The Status ◽  
Grade 3

e13540 Background: A number of patients with locally advanced cervical cancer will recur despite presenting initial response to chemoradiation. Single-nucleotide polymorphisms (SNP) of DNA repair genes have been found to be predictors of efficacy of chemotherapy and radiotherapy. Methods: We evaluated the presence of SNP in ERCC1, BRAC 1 and 2 genes. We analysed paraffin-embedded biopsies from patients who had relapsed after receiving treatment with chemoradiation, for SNP of the mentioned genes. The status of the alleles wild type (wt) or at least 1 SNP was compared with time to progression (TTP) and toxicity. Results: 90 patients who experience recurrence of their cervical cancer were included in the analysis. Of those, we only could obtain evaluable tumour from 43 patients. Median age: 52.5 yrs (31-81). Histology: 32 squamous cell, 8 adenocarcinoma, 3 adenosquamous. One SNP in BRAC1 (rs12516) was found to be significantly associated with better TTP for the mutant variant compared to the wild-type (124 m. vs. 14 m.). Furthermore, all six patients who presented with severe (grade 3-4) toxicity had this wild-type SNP (rs12516) in BRAC1 gene. Conclusions: We have identified a SNP which confers better outcome in patients with cervical cancer. Further analysis need to be done to determine its relation to radiation-induced toxicity in this group of patients.

scholarly journals Associations between single nucleotide polymorphisms in the FAS pathway and acute kidney injury

Critical Care ◽  
2015 ◽  
Vol 19 (1) ◽  
Author(s):  
Pavan Bhatraju ◽  
Christine Hsu ◽  
Paramita Mukherjee ◽  
Bradford J. Glavan ◽  
Amber Burt ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Single Nucleotide Polymorphisms ◽  
Kidney Injury ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Fas Pathway

Association of genetic polymorphism of cytokines and antioxidant enzymes with the development of asbestosis

2020 ◽  
Vol 60 (12) ◽  
pp. 898-903
Author(s):  
Lyudmila P. Kuzmina ◽  
Anastasiya G. Khotuleva ◽  
Evgeniy V. Kovalevsky ◽  
Nikolay N. Anokhin ◽  
Iraklij M. Tskhomariya
Keyword(s):  
Antioxidant Enzymes ◽  
Genetic Polymorphism ◽  
Genetic Predisposition ◽  
Risk Groups ◽  
Dust Exposure ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Gstp1 Gene ◽  
Polymorphic Variants

Introduction. Various industries widely use chrysotile asbestos, which determines the relevance of research aimed at the prevention of asbestos-related diseases. It is promising to assess the role of specific genes, which products are potentially involved in the development and regulation of certain links in the pathogenesis of asbestosis, forming a genetic predisposition to the disease. The study aims to analyze the presence of associations of genetic polymorphism of cytokines and antioxidant enzymes with asbestosis development. Materials and methods. Groups were formed for examination among employees of OJSC "Uralasbest" with an established diagnosis of asbestosis and without lung diseases. For each person included in the study, dust exposure doses were calculated considering the percentage of time spent at the workplace during the shift for the entire work time. Genotyping of single nucleotide polymorphisms of cytokines IL1b (rs16944), IL4 (rs2243250), IL6 (rs1800795), TNFα (rs1800629) and antioxidant enzymes SOD2 (rs4880), GSTP1 (rs1610011), CAT (rs1001179) was carried out. Results. The authors revealed the associations of polymorphic variants A511G IL1b gene (OR=2.457, 95% CI=1.232-4.899) and C47T SOD2 gene (OR=1.705, 95% CI=1.055-2.756) with the development of asbestosis. There was an increase in the T allele IL4 gene (C589T) frequency in persons with asbestosis at lower values of dust exposure doses (OR=2.185, 95% CI=1.057-4.514). The study showed the associations of polymorphism C589T IL4 gene and C174G IL6 gene with more severe asbestosis, polymorphism A313G GSTP1 gene with pleural lesions in asbestosis. Conclusion. Polymorphic variants of the genes of cytokines and antioxidant enzymes, the protein products directly involved in the pathogenetic mechanisms of the formation of asbestosis, contribute to forming a genetic predisposition to the development and severe course of asbestosis. Using the identified genetic markers to identify risk groups for the development and intense period of asbestos-related pathology will optimize treatment and preventive measures, considering the organism's characteristics.

scholarly journals Incidence and Outcomes of Acute Kidney Injury in Patients Admitted to Hospital With COVID-19: A Retrospective Cohort Study

2021 ◽  
Vol 8 ◽  
pp. 205435812110277
Author(s):  
Tyler Pitre ◽  
Angela (Hong Tian) Dong ◽  
Aaron Jones ◽  
Jessica Kapralik ◽  
Sonya Cui ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Kidney Injury ◽  
Cohort Study ◽  
Hospital Mortality ◽  
Disease Severity ◽  
Retrospective Cohort Study ◽  
Odds Ratio ◽  
Retrospective Cohort ◽  
Kidney Injury ◽  
Icu Admission

Background: The incidence of acute kidney injury (AKI) in patients with COVID-19 and its association with mortality and disease severity is understudied in the Canadian population. Objective: To determine the incidence of AKI in a cohort of patients with COVID-19 admitted to medicine and intensive care unit (ICU) wards, its association with in-hospital mortality, and disease severity. Our aim was to stratify these outcomes by out-of-hospital AKI and in-hospital AKI. Design: Retrospective cohort study from a registry of patients with COVID-19. Setting: Three community and 3 academic hospitals. Patients: A total of 815 patients admitted to hospital with COVID-19 between March 4, 2020, and April 23, 2021. Measurements: Stage of AKI, ICU admission, mechanical ventilation, and in-hospital mortality. Methods: We classified AKI by comparing highest to lowest recorded serum creatinine in hospital and staged AKI based on the Kidney Disease: Improving Global Outcomes (KDIGO) system. We calculated the unadjusted and adjusted odds ratio for the stage of AKI and the outcomes of ICU admission, mechanical ventilation, and in-hospital mortality. Results: Of the 815 patients registered, 439 (53.9%) developed AKI, 253 (57.6%) presented with AKI, and 186 (42.4%) developed AKI in-hospital. The odds of ICU admission, mechanical ventilation, and death increased as the AKI stage worsened. Stage 3 AKI that occurred during hospitalization increased the odds of death (odds ratio [OR] = 7.87 [4.35, 14.23]). Stage 3 AKI that occurred prior to hospitalization carried an increased odds of death (OR = 5.28 [2.60, 10.73]). Limitations: Observational study with small sample size limits precision of estimates. Lack of nonhospitalized patients with COVID-19 and hospitalized patients without COVID-19 as controls limits causal inferences. Conclusions: Acute kidney injury, whether it occurs prior to or after hospitalization, is associated with a high risk of poor outcomes in patients with COVID-19. Routine assessment of kidney function in patients with COVID-19 may improve risk stratification. Trial registration: The study was not registered on a publicly accessible registry because it did not involve any health care intervention on human participants.

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