Preemptive NUDT15 genotyping: redefining the management of patients with thiopurine-induced toxicity

2018 ◽  
Vol 33 (1) ◽  
pp. 57-60 ◽  
Author(s):  
Swarup A.V. Shah ◽  
Minal U. Paradkar ◽  
Devendra C. Desai ◽  
Tester F. Ashavaid
Keyword(s):  
Strong Association ◽  
Amplification Refractory Mutation System ◽  
Dose Requirement ◽  
Asian Patients ◽  
Thiopurine Therapy ◽  
Individual Variations ◽  
Significant Difference ◽  
Mutation System ◽  
Risk Patients

AbstractBackground:Thiopurine methyltransferase (TPMT) gene variants have achieved limited success in predicting the outcome of thiopurine therapy, which shows wide inter-individual variations. The literature indicates a strong association between theNUDT15gene variant and thiopurine-induced toxicity in Asian patients. The present study intends to explore the role of theNUDT15variant (C415T) in Indian patients on thiopurine therapy.Methods:NUDT15andTPMTgenotyping were performed using amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) and the restriction fragment length polymorphism (RFLP) technique.Results:Of 370 samples received forTPMTtesting, 206 samples were available forNUDT15genotyping. TheNUDT15risk allele frequency was 10.7%, with the frequency of wild, heterozygous and mutant genotypes being 80.6%, 17.5% and 1.9%, respectively.TPMTvariants were seen in 13 of 370 (3.5%) patients, whereas theNUDT15variant was seen in 40 of 206 (19.4%) patients. Thiopurine-induced toxicity information was available for 101 patients, among whom 10 developed leukopenia and all harbored theNUDT15variant (p<0.0001).NUDT15was clinically more relevant thanTPMTin terms of sensitivity and specificity, as well as with a statistically significant difference in thiopurine dose requirement for patients with theNUDT15variant.Conclusions:A preemptiveNUDT15genotyping approach can therefore help identify high-risk patients (NUDT15C415T positive) who could benefit from thiopurine dose reduction, thereby preventing fatal thiopurine-induced toxicity.

Predictive role of single nucleotide polymorphism (rs11614913) in the development of breast cancer in Pakistani population

2020 ◽  
Vol 17 (3) ◽  
pp. 213-227
Author(s):  
Mushtaq Ahmad ◽  
Aftab Ali Shah
Keyword(s):  
Breast Cancer ◽  
Single Nucleotide Polymorphism ◽  
Target Genes ◽  
Amplification Refractory Mutation System ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Significant Difference ◽  
Mutation System ◽  
Predictive Role

Aim: miRNAs play an important role in breast cancer (BC). Variations in miRNAs influence their maturation, expression and consequently regulation of their target genes. Materials & methods: In this study, single nucleotide polymorphism rs11614913 was genotyped in BC patients (n = 300) and 230 controls by employing tetra primer amplification refractory mutation system PCR and Sanger sequencing (Macrogen Korea). Results: A significant difference was observed in the genotypes through co-dominant ( χ2.#x00A0;= 42.03; p < 0.0001), additive (odds ratio [OR] = 0.6441 [0.4887–0.8490, 95% confidence interval]; p < 0.0019), dominant (OR = 0.3996 [0.2809–0.5686], p < 0.0001) and recessive (OR = 0.2993 [0.1220–0.7347], p < 0.009) statistical models showed decreased risk association of C allele with BC. Conclusion: Females having CT genotype are at higher risk of BC as compared with those having CC genotype.

scholarly journals Evaluation of Transcription Factor 7 like 2 polymorphisms and haplotypes in risk of Type 2 Diabetes

2016 ◽  
Vol 24 (4) ◽  
pp. 423-430 ◽  
Author(s):  
Ramin Saravani ◽  
Zahra Irani ◽  
Hamid Reza Galavi
Keyword(s):  
Type 2 Diabetes ◽  
Transcription Factor ◽  
Haplotype Analysis ◽  
Amplification Refractory Mutation System ◽  
Chronic Disorder ◽  
Increased Risk ◽  
Significant Difference ◽  
Mutation System ◽  
Control Study

Abstract Type 2 diabetes (T2D) is a chronic disorder with different genetics and environmental factors. It is one of growing diseases in the world. Previous studies show association between Transcription Factor 7 Like2 (TCF7L2) and T2D. The current study set to evaluate the relation between TCF7L2 polymorphisms and T2D in Southeast Iran. The present case-control study was done on 250 T2D and 250 healthy controls (HCs). For genotyping polymorphisms TCF7L2 (rs11196205) and (rs4132670) Amplification-Refractory Mutation System-Polymers Chain Reaction (ARMS-PCR) was used. The results showed frequency rates of GC and CC genotypes increased in patients compared to controls (31% vs. 6% and 55% vs. 8%, respectively), showing a statistically significant difference (OR=2.67(1.37-5.21), P<0.05 and OR=3.31(1.92-5.71), P< 0.05, respectively). The C allele was associated with an increased risk of T2D, with the frequency of 28% and 11% in patients and controls, respectively (OR=3.11 (2.22-4.37), P< 0.05). Another Polymorphism of this gene TCF7L2 (rs4132670) was not associated with T2D. Furthermore, the haplotype analysis revealed that rs11196205C/rs4132670C and rs11196205C/rs4132670T are risk factors against T2D (OR=2.08 (1.49-2.86, P<0.05 and OR=1.72 (1.06-2.78) P<0.05, respectively). The findings demonstrated that TCF7L2 (rs11196205) genotypes GC, CC, and allele (C) confer risk for susceptibility to T2D.

Determination of a T/G polymorphism at nucleotide 3206 of the apolipoprotein C III gene by amplification refractory mutation system

1994 ◽  
Vol 40 (12) ◽  
pp. 2235-2239 ◽  
Author(s):  
M Y Tsai ◽  
N Q Hanson ◽  
K R Copeland ◽  
I Beheshti ◽  
U Garg
Keyword(s):  
Epidemiological Studies ◽  
Amplification Refractory Mutation System ◽  
Chain Reaction ◽  
Apolipoprotein C ◽  
Significant Difference ◽  
Mutation System ◽  
Polymerase Chain ◽  
Exon 4 ◽  
And Control

Abstract We used the amplification refractory mutation system (ARMS)--a polymerase-chain-reaction-based method--to determine the 3206 T-to-G polymorphism on exon 4 of the apolipoprotein (apo) C III gene. Apo C III is an inhibitor of the enzyme lipoprotein lipase (EC 3.1.1.34). Previous studies have demonstrated that a polymorphism at nucleotide 3175 on exon 4 of this gene is associated with hypertriglyceridemia. We studied 45 hypertriglyceridemic and 46 age-matched controls for the 3206 T-to-G polymorphism. The results showed a significant difference in the distribution of the genotypes with respect to this allele between the hypertriglyceridemic and control individuals. We also determined the presence of the SacI site at nucleotide 3175 in these same individuals and found no significant difference in SacI genotypes between the two groups. This study reaffirms the usefulness of ARMS as a simple, reliable method for detecting mutations and polymorphisms in clinical and epidemiological studies.

scholarly journals Methylenetetrahydrofolate Reductase C677T and A1298C Mutations in Women with Recurrent Spontaneous Abortions in the Northwest of Iran

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ahmad Poursadegh Zonouzi ◽  
Nader Chaparzadeh ◽  
Mehrdad Asghari Estiar ◽  
Mahzad Mehrzad Sadaghiani ◽  
Laya Farzadi ◽  
...  
Keyword(s):  
Restriction Fragment Length Polymorphism ◽  
Methylenetetrahydrofolate Reductase ◽  
Fragment Length Polymorphism ◽  
Gene Mutations ◽  
Mthfr Gene ◽  
Amplification Refractory Mutation System ◽  
Healthy Controls ◽  
Significant Difference ◽  
Mutation System ◽  
Restriction Fragment Length

Introduction. Recurrent spontaneous abortion (RSA) is a significant obstetrical complication that may occur during pregnancy. Various studies in recent years have indicated that two common mutations (C677T and A1298C) of the methylenetetrahydrofolate reductase (MTHFR) gene are risk factor for RSA. This study was carried out to determine the influence of (C677T and A1298C) of the methylenetetrahydrofolate reductase (MTHFR) gene mutations with RSA. Materials and Methods. A total of 139 women were included in this study: 89 women with two or more consecutive miscarriages and 50 healthy controls. Total genomic DNA was isolated from blood leukocytes. To determine the frequency of the two common C677T and A1298C MTHFR gene mutations in the patients and controls, we used two methods, amplification refractory mutation system-PCR and PCR-restriction fragment length polymorphism. Results. There is no significant difference in the prevalence of 677T/T genotype among women with RSA and healthy controls (). Also no statistically significant difference in the frequency of A1298C MTHFR gene mutation was detected between the two groups ( ). Conclusion. In conclusion, the results indicate that the Amplification Refractory Mutation System-PCR method was in complete concordance with the results obtained by standard PCR-restriction fragment length polymorphism method. The results also show no significant difference in MTHFR C677T/A1298C genotype distribution among the two groups; therefore, further studies on larger population and other genetic variants to better understand the pathobiology of RSA are needed.

scholarly journals The Role of Rapid Endoscopy for High-Risk Patients with Acute Nonvariceal Upper Gastrointestinal Bleeding

2007 ◽  
Vol 21 (7) ◽  
pp. 425-429 ◽  
Author(s):  
Laura E Targownik ◽  
Sanjay Murthy ◽  
Leila Keyvani ◽  
Shauna Leeson
Keyword(s):  
High Risk ◽  
Gastrointestinal Bleeding ◽  
Upper Gastrointestinal Bleeding ◽  
Tertiary Care ◽  
High Risk Patients ◽  
Transfusion Requirements ◽  
Significant Difference ◽  
Risk Patients ◽  
Upper Gastrointestinal

BACKGROUND: Performance of endoscopy within 24 h is recommended for patients with acute nonvariceal upper gastrointestinal bleeding (ANVUGIB). It is unknown whether performing endoscopy early within this 24 h window is beneficial for clinically high-risk patients.METHODS: A retrospective review was performed to identify patients presenting to two tertiary care centres with ANVUGIB and either systolic blood pressure lower than 100 mmHg or heart rate greater than 100 beats/min on presentation between 1999 and 2004. Patients receiving endoscopy within 6 h (rapid endoscopy [RE]) were compared with patients undergoing endoscopy between 6 h and 24 h (early endoscopy [EE]). The primary outcome measure was the development of any adverse bleeding outcome (rebleeding, surgery for control of bleeding, in-hospital mortality or readmission within 30 days for ANVUGIB).RESULTS: There were 169 patients who met the entry criteria (77 RE patients and 92 EE patients). There was no significant difference in the development of any adverse bleeding outcomes between RE and EE patients (25% RE versus 23% EE, difference between groups 2%, 95% CI −9% to 13%). Transfusion requirements and length of hospital stay also did not differ between the comparator groups. RE was not associated with fewer adverse outcomes, even after adjusting for confounders.CONCLUSION: For clinically high-risk ANVUGIB patients, performing endoscopy within 6 h of presentation is no more effective than performing endoscopy between 6 h and 24 h after presentation. The role of RE in high-risk ANVUGIB patients requires further delineation in a prospective fashion.

scholarly journals Prevalence of BRAF V600E Mutation in the Iranian Patients with Hairy Cell Leukemia: A Retrospective Study

2021 ◽  
Vol 6 (2) ◽  
pp. 141-145
Author(s):  
Mojtaba Karimi ◽  
Ahmad Monabbati ◽  
Nasibeh Sargazi Moghadam
Keyword(s):  
Hairy Cell Leukemia ◽  
Clinical Laboratory ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Amplification Refractory Mutation System ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Significant Difference ◽  
Mutation System ◽  
Embedded Blocks

Objective: BRAF V600E mutation has several implications in hairy cell leukemia (HCL). The prevalence of This mutation has been investigated in various populations, but not in Iran. In this study, we evaluated the prevalence of BRAF V600E mutation in an Iranian HCL population as well as its association with the patients’ characteristics.Methods: In a retrospective (archival) study, 20 HCL patients with the confirmed immunophenotypic and morphologic diagnosis were included. Paraffin-embedded blocks of bone marrow aspirate were used to investigated BRAF V600E mutation using amplification refractory mutation system (ARMS) PCR. Demographic, clinical, laboratory, and immunophenotypic characteristics of patients were extracted from the patients medical profiles.Result: BRAF V600E mutation was present in 17 (85%) HCL patients and absent in three (15%) patients. The mean age of the patients was 44.76 ± 8.69 years in mutation-positive and 62.33 ± 8.69 in mutation-negative patients. This difference was statistically significant (p=0.013). No significant difference was found between the laboratory indices of the mutation-positive and mutation-negative groups. The clinical, morphologic, and immunophenotypic characteristics of the two groups were also statistically comparable.Conclusion: BRAF V600E mutation is present in the majority of the Iranian HCL patients and is associated with younger age of presentation.

Studying Cytotoxic T-lymphocyte- Associated Antigen-4 (CTLA-4) gene Polymorphism in a Sample of Iraqi Women with Polycystic Ovarian Syndrome

2019 ◽  
pp. 1-6
Keyword(s):  
Gene Polymorphism ◽  
Polycystic Ovarian Syndrome ◽  
Cytotoxic T Lymphocyte ◽  
Reproductive Age ◽  
Amplification Refractory Mutation System ◽  
Low Grade ◽  
Metabolic Disturbances ◽  
Mutation System ◽  
Ovarian Syndrome

Polycystic ovarian syndrome (PCOS) considers as the most common disorder among women during reproductive age. Its common features involve hyperandrogenism, chronic anovulation, and weight gain. Till now, the pathogenesis of PCOS stay unknown, and there is evidence considered PCOS as a low-grade inflammatory disease. Polycystic ovarian syndrome is associated with a variety of endocrine and metabolic disturbances. The present study was designed to detect the role of (CTLA-4) gene polymorphism (rs733618) with PCOS. A total of 60 PCOS patients and 30 healthy women, matching in average age and body mass index (BMI), were enrolled in this study. Patients with PCOS were attend to AL - Nahrain University High Institute for Infertility Assisted Reproductive Technology, in Baghdad between Septembers to December/2018. Blood samples were aspirated from both groups to detection (CTLA-4) gene polymorphism (rs733618) by tetra-primer amplification-refractory mutation system based on real time polymerase chain reaction (ARMS-qPCR). The obtained results revealed normal genotyping for both groups. The result of current study confirms that there is no role of (CTLA-4) gene polymorphism (rs 733618) in PCOS.

Investigation of the impact of an ADCY2 polymorphism as a predictive biomarker in bipolar disorder, suicide tendency and response to lithium carbonate therapy: the first report from Iran

2020 ◽  
Vol 21 (14) ◽  
pp. 1011-1020
Author(s):  
Sara Sadat Aghabozorg Afjeh ◽  
Jamal Shams ◽  
Safar Hamednia ◽  
Behzad Boshehri ◽  
Amir Olfat ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Suicide Ideation ◽  
Lithium Carbonate ◽  
Predictive Biomarker ◽  
Amplification Refractory Mutation System ◽  
Cerebral Endothelium ◽  
Mutation System ◽  
Bipolar Patients ◽  
The Impact

High rates of mortality due to both suicide and medical comorbidities in bipolar patients can be decreased through the administration of lithium, which affects the cerebral endothelium as well as neurons. To investigate the role of ADCY2 in risk of bipolar disorder, we genotyped the ADCY2 rs2290910 in bipolar patients and healthy controls using amplification refractory mutation system PCR. This polymorphism was associated with risk of bipolar disorder (odds ratio [OR]: 0.430; 95% CI: 0.296–0.624; p = 0.001). The C allele was more frequent in suicide ideation group compared other groups (OR: 2.7; 95% CI: 1.386–5.302; p = 0.004). The T allele was more frequent in suicide attempt group compared with suicide ideation group (OR: 0.238; 95% CI: 0.111–0.509; p = 0.001).

scholarly journals No Association ofPTGDR−441C/TPolymorphism with Asthma in a North Indian Population

2011 ◽  
Vol 31 (6) ◽  
pp. 353-359 ◽  
Author(s):  
Niti Birbian ◽  
Jagtar Singh ◽  
Surinder Kumar Jindal ◽  
Amit Joshi ◽  
Navneet Batra
Keyword(s):  
Indian Population ◽  
D2 Receptor ◽  
Promoter Polymorphism ◽  
North India ◽  
Amplification Refractory Mutation System ◽  
Prostaglandin D2 ◽  
North Indian Population ◽  
Mutation System ◽  
Prevalent Disease

Background:Asthma is the most prevalent disease in India according to the national survey conducted by NFHS 2 in 1998–399. Prostaglandin D2 (PGD2) is a bronchoconstriction inducing metabolite of arachidonic acid in the mast cells, which is produced on exposure to allergens and acts as a ligand for the Prostaglandin D2 Receptor (PTGDR). Polymorphisms in thePTGDRgene have been suggested to be involved in the mechanism of asthma.Objective:This is the first study conducted in India, investigating the role ofPTGDR−441C/Tpromoter polymorphism in asthma pathogenesis.Methods:A case-control study was performed with a total of 992 subjects, including 410 adult asthmatics and 582 healthy controls from regions of North India. ThePTGDR−441C/Tpolymorphism was genotyped by Tetra-Primer Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra-Primer ARMS PCR).Results:Statistical analysis of the results between asthma cases and controls for thePTGDR−441C/Tpolymorphism showed Chi2(χ2) = 0.29, OR = 0.95, 95% CI (0.70–1.15) andp= 0.599. Neither the genotypic nor the allelic frequencies observed for thePTGDR−441C/Tpolymorphism, were significantly associated with asthma or asthma phenotypes.Conclusions:ThePTGDR−441C/Tpolymorphism is not associated with asthma or its phenotypes in the studied North Indian population.

Association of BTNL2 gene single nucleotide polymorphism with knee osteoarthritis

2021 ◽  
Vol 25 (2) ◽  
pp. 89-95
Author(s):  
S. S. Sahoo ◽  
O. K. Choudhari ◽  
J. Bhadra ◽  
B. C. Kabi
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Knee Osteoarthritis ◽  
Indian Population ◽  
Amplification Refractory Mutation System ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Genotypic Distribution ◽  
Mutation System ◽  
Hardy Weinberg Equilibrium

Relevance. Osteoarthritis (OA) is one of the chronic debilitating condition mostly seen in the aged population. The etiology behind the OA is multifactorial and the exact cause of the disease often remains uncertain. Apart from the conventional risk factors, there are the speculations of role of genetics playing a pivotal role in the causation of OA. The available literature showed BTNL2 gene polymorphism association with risk of Osteoarthritis whether the same relation is present in north Indian population needs to be elucidated. Objective. To find the association between single nucleotide polymorphism (SNP) (rs10947262) in BTNL2 gene and the susceptibility in knee Osteoarthritis (OA) subjects from northern Indian population. Materials and Methods. Blood samples of 100 patients of knee osteoarthritis and 100 healthy subjects were collected after institutional ethical clearance and participants consent. The BTNL2 gene fragment was amplified using Amplification Refractory Mutation System (ARMS-PCR) with predesigned primers after DNA extraction. The corresponding product bands were identified on the gel electrophoresis for 200 samples and the results were statistically analyzed. Results and Discussion. The genotypic distribution of the SNP followed Hardy-Weinberg Equilibrium. The genotype frequency analysis of the polymorphism was statistically significant (2=7.788; P=0.005) with Odds Ratio of CT+TT/CC: OR=2.303; P=0.008 revealing association of BTNL2 polymorphism with risk of Knee Osteoarthritis. Conclusion. The SNP (rs10947262) in the BTNL2 gene region is associated with risk of knee osteoarthritis.

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