scholarly journals GLU298ASP and 4G/5G Polymorphisms and the Risk of Ischemic Stroke in Young Individuals

2015 ◽  
Vol 42 (5) ◽  
pp. 310-316 ◽  
Author(s):  
Juan Carlos Esparza-García ◽  
David Santiago-Germán ◽  
María Guadalupe Valades-Mejía ◽  
Jesus Hernández-Juárez ◽  
Eberth Aguilar-Sosa ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Allele Frequency ◽  
Plasminogen Activator Inhibitor ◽  
Mexican Population ◽  
Genotype Distribution ◽  
Plasminogen Activator Inhibitor 1 ◽  
Increased Risk ◽  
Significant Difference ◽  
And Gender ◽  
Endothelial Nitric Oxide

AbstractBackground: Polymorphisms in the endothelial nitric oxide synthase (eNOS) and in the plasminogen activator inhibitor -1 (PAI-1) genes have been implicated in stroke pathogenesis but results are still controversial. The aim of this study was to examine the possible contribution of Glu298Asp in the eNOS and 4G/5G in the PAI-1polymorphisms with ischemic stroke in a young Mexican population. Materials and Methods: In a case-control study, conducted between January 2006 and June 2010, 204 patients ≤45 years of age with ischemic stroke and 204 controls matched by age and gender, were recruited. The Glu298Asp and 4G/5G polymorphisms were determined in all participants by polymerase chain reaction-restriction fragment length polymorphism. Results: There was a significant difference in the Glu298Asp genotype distribution (P=0.001) and allele frequency between the two groups (P=0.001). The 4G/5G genotype distribution (P=0.40) and the allele frequency was similar between groups; (P=0.13). There were independent factors for ischemic stroke: Asp carriage (GluAsp+AspAsp) (P=0.02); smoking (P=0.01); hypertension (P=0.03), and familial history of atherothrombotic disease (P=0.04). Conclusions: The Asp allele from the Gu298Asp gene represents an independent risk factor for ischemic stroke in a young Mexican population. In contrast, the 4G/5G was not associated with an increased risk for this disease in the same group of patients, as previously has been demonstrated in other populations.

scholarly journals Genetic Polymorphisms Associated with Thrombotic Disease Comparison of Two Territories: Myocardial Infarction and Ischemic Stroke

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Irma Isordia-Salas ◽  
Manuel Martínez-Marino ◽  
Paolo Alberti-Minutti ◽  
María Tania Ricardo-Moreno ◽  
Ricardo Castro-Calvo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ischemic Stroke ◽  
Family History ◽  
Allele Frequency ◽  
Genetic Polymorphisms ◽  
Mexican Population ◽  
Genotype Distribution ◽  
Significant Difference ◽  
History Of ◽  
Atherothrombotic Disease

Background and Purpose. The thrombin-activatable fibrinolysis inhibitor (TAFI) is an important inhibitor of fibrinolysis and plays a critical role in the pathogenesis of arterial thrombosis; genetic polymorphisms of the TAFI gene affect its activity and increase the risk of thrombosis. Moreover, studies in young patients are still scarce. The aim was to examine the contribution of the Thr325Ile and Ala147Thr polymorphisms with ST acute myocardial infarction (STEMI) or idiopathic ischemic stroke (IIS) in the young Mexican population. Methods. A total of 244 patients with STEMI ≤45 years of age and 244 controls. In a second study, 250 patients with IIS ≤45 years of age were recruited, including 250 controls. In both studies, cases and controls were matched by age and sex. The polymorphisms were determined in all participants by PCR-RFLP. Results. There was significant difference in the Thr325Ile genotype distribution (P=0.001) and allele frequency (P=0.001) between STEMI and control groups, but no difference in the Ala147Thr genotype distribution (P=0.24) and allele frequency (P=0.46), neither in the Thr325Ile genotype distribution (P=0.25) nor in the Ala147Thr genotype distribution (P=0.46) or their allele frequencies; there was significant difference between IIS and the control group. There were independent factors for STEMI: the Ile allele (P=0.01), type 2 diabetes mellitus (P=0.001), hypertension (P=0.001), smoking (P=0.001), dyslipidemia (P=0.001), and family history of atherothrombotic disease (P=0.001). The independent factors for IIS were hypertension (P=0.001), smoking (P<0.01), and family history of atherothrombotic disease (P<0.01). Conclusions. The Thr325Ile polymorphism, but no Ala147Thr polymorphism, represents an independent risk factor for STEMI in the young Mexican population.

scholarly journals An Interdependence between Estrogen Receptor 1 Gene Polymorphisms and Susceptibility to Breast Cancer

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Maryam Saneipour ◽  
Abdolkarim Sheikhi ◽  
Abbas Moridnia
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Allele Frequency ◽  
Genetic Alterations ◽  
Recessive Model ◽  
Control Group ◽  
Genotype Distribution ◽  
Increased Risk ◽  
Significant Difference ◽  
Estrogen Receptor 1

Background: Breast cancer (BC) is the most common malignant tumor in women around the world. Genetic factors do play a vital role in the development and progression of BC. Genetic alterations in the ESR1 (estrogen receptor 1) gene can lead to estrogen dysfunction and increased risk for BC. Nevertheless, due to genetic diversity, the information from different studies is contradictory and controversial. Objectives: This study aimed to investigate the potential relationship between the rs1801132 and rs2234693 single nucleotide polymorphism (SNPs) of the ESR1 gene with susceptibility to BC in the Iranian population. Methods: The genotyping of the rs2234693 and rs1801132 SNPs was assessed in 63 BC patients referred to Imam Hasan Mojtaba Center, which is a charity-based foundation for cancer care in Dezful, Iran, from March 2018 to November 2019. Also, 65 healthy women were selected as a control group. The genotyping of the SNPs was performed using the high-resolution melting (HRM) technique and confirmed by DNA sequencing. Results: The genotype distribution and allele frequency of the rs2234693 SNP were significantly different in BC patients compared to the control group (genotype frequency with P = 0.018 and allele frequency with P = 0.004, OR = 2.085, 95% CI = 1.253 -3.468). In genetic models, rs2234693 increased BC risk in recessive model (P = 0.005, OR = 2.813, 95% CI = 1.363 - 5.802). However, there was no significant difference regarding genotype distribution of the rs1801132 SNP between the BC patients and controls. Conclusions: Our results showed that the CC genotype of the rs2234693 SNP is significantly associated with BC. Accordingly, it can be suggested that the rs2234693 SNP be considered for susceptibility to BC.

Association of MDM2 Gene Polymorphisms SNP285 and 309 with Myelodysplastic Syndromes (MDS) Susceptibility and Outcome.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2823-2823
Author(s):  
Kathy L. McGraw ◽  
Lan Min Zhang ◽  
William Fulp ◽  
Hui-Yi Lin ◽  
Andres Jerez ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Response Rate ◽  
Disease Onset ◽  
Response Duration ◽  
Negative Regulator ◽  
Genotype Distribution ◽  
Healthy Controls ◽  
Genotype Frequencies ◽  
Increased Risk ◽  
Significant Difference

Abstract Abstract 2823 Background: Mutations in TP53, or less often its regulators, increases risk for malignant transformation. Murine double minute protein 2 (MDM2), an E3 ubiquitin ligase, targets p53 for proteasomal degradation and is the most well studied negative regulator of p53. Recent investigations have highlighted the emerging importance of p53 in MDS. Haploinsufficiency for ribosomal protein S14 in deletion 5q MDS liberates free ribosomal proteins that bind to and promote degradation of MDM2, thereby activating p53 in erythroid precursors. A single nucleotide polymorphism (SNP) in an MDM2 promoter (SNP309) is linked to younger age of onset of several solid tumors and an increased risk for acute myeloid leukemia (AML) [Knappskog and Lonning. 2011. Transcription 2:207, Xiang et al. 2009. Leuk Res. 33:1454]. The thymine (T) to guanine (G) substitution introduces an additional Sp1 transcription factor binding site causing upregulation of MDM2 transcription. A second SNP in this promoter (SNP285) has also been linked to cancer susceptibility, where a guanine (G) to cytosine (C) exchange is associated with decreased ovarian and breast cancer risk (Knappskog and Lonning. 2011. Oncotarget. 2:251). The C-allele of SNP285 has diminished Sp1 promoter binding compared to the G-allele decreasing MDM2 expression. In this study we investigated genotype distribution of MDM2 SNPs in del(5q) and non-del(5q) MDS patients and compared results to healthy controls. Methods and Results: Using Sanger sequencing, we compared allele and genotype frequencies for SNP285 and SNP309 in 155 healthy controls, 97 non-del(5q), and 119 del(5q) MDS patients. For SNP285, we found no significant difference in genotype or allele frequency among non-del(5q) or del(5q) cases compared to controls (p=0.25 and 0.26, respectively). Although there was no difference in age at diagnosis by genotype in del(5q) MDS (p=0.82), there was a significant difference among non-del(5q) MDS cases [p<0.01, mean (range) for GC:80.8y (75–89) and GG:68.9y (27–91)], however, the frequency of the GC genotype was low [n=5, non-del(5q); n=11, del(5q)] with no CC genotype cases. For SNP309, there was no difference in allele frequency (p=0.68), however genotype frequency differed between controls, non-del5q, and del5q MDS (p=0.06). The genotype distribution was significantly different between non-del(5q) and del(5q) MDS (p=0.01). SNP309 genotype frequencies for controls, non-del(5q), and del(5q) MDS were GG:17.3%, 22.7%, 10.1%; TG: 42.9%, 37.1%, 53.8%; TT: 39.7%, 40.2%, 36.1%, respectively. We found no difference in age of disease onset by SNP309 genotype in either non-del(5q) or del(5q) cases (p=0.08 and 0.97, respectively). There was no significant relationship between SNP285 genotype and IPSS (p=1.0), cytogenetic risk (p=0.66), or WHO classification (p=0.16) in non-del(5q) or del(5q) cases (p=1.0, 0.78, and 0.60, respectively). Similar results were observed for SNP309 [p=0.85, 0.39, and 0.68 for non-del(5q); p= 0.06, 0.98, 0.27 for del(5q), respectively]. For SNP285 there was no difference in overall survival (OS) by genotype in either non-del(5q) (p=0.65) or del(5q) MDS (p=0.72). Progression free survival (PFS) also did not differ by genotype in non-del(5q) (p=0.82) or del(5q) (p=0.58) patients. There was a significant difference in LEN response rate in del(5q) MDS (p=0.04, non-responders: 23.8% GC and 76.2% GG, responders: 4.9% GC and 95.1% GG), however, genotype did not influence response duration (p= 0.40). For SNP309, there were no significant difference in OS by genotype (p=0.42), PFS (p=0.78), LEN response rate (p=0.17), or response duration in del(5q) MDS (p=0.65). In non-del(5q), there was no difference in OS (p=0.42), LEN response rate (p=0.91), or response duration (p=0.47). However, we found a significant difference in PFS by genotype (p=0.03) with more prolonged PFS in patients with the heterozygous TG genotype (60 mo PFS: GG 55.3%, TT 54.1%, and TG 81.7%). Finally, we found no difference in chromosome 5 deletion size or deletion location in del(5q) MDS according to SNP309 genotype. Conclusions: MDM2 SNP309 may be linked to MDS susceptibility, as well as LEN responsiveness and PFS in del(5q) and non-del(5q) MDS, respectively. These data warrant validation in a larger patient cohort. Investigation of the interaction between MDM2 SNPs and the well described TP53 R72P SNP is underway. Disclosures: List: Celgene: Consultancy.

The Nonsynonymous Single-Nucleotide Polymorphisms in Codon 31 of p21 Gene and the Susceptibility to Cervical Cancer in Chinese Women

2009 ◽  
Vol 19 (6) ◽  
pp. 1011-1014 ◽  
Author(s):  
Qifang Tian ◽  
Weiguo Lu ◽  
Huaizeng Chen ◽  
Feng Ye ◽  
Xing Xie
Keyword(s):  
Cervical Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Allele Frequency ◽  
Chinese Women ◽  
Host Susceptibility ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Significant Difference

Background:It was suggested that single-nucleotide polymorphisms in p21 codon 31 seem to be associated with a variety of human malignancies; very few studies have focused on the association between p21 codon 31 polymorphisms and cervical cancer. This study explored whether p21 codon 31 nonsynonymous single-nucleotide polymorphisms might be associated with an increased risk of cervical cancer development among Chinese women.Methods:Peripheral blood samples were obtained from patients with cervical cancer (n = 317) and healthy controls (n = 353) for detecting the biallelic polymorphisms at codon 31 of p21 gene by the mismatch amplification mutation assay-polymerase chain reaction. Cervix brush-off samples were obtained from patients with cervical squamous cell carcinoma (SCC) and controls for detection of high-risk human papillomavirus (HR-HPV).Results:The AGA (Arg) allele frequency in patients with cervical SCCs was significantly higher than that in controls. AGA/AGA and AGA/AGC genotypes were more frequently found in cervical SCCs than in controls. There was no significant difference of allele frequency or genotype distribution between cervical adenocarcinomas and controls, or between HR-HPV-positive and HR-HPV-negative groups.Conclusions:p21 Codon 31 with AGA (Arg) allele is a genetic risk factor of cervical SCC, and the increased risk is probably not caused by increasing host susceptibility to HR-HPV infection.

A Specific Immunologic Assay for Functional Plasminogen Activator Inhibitor 1 in Plasma – Standardized Measurements of the Inhibitor and Related Parameters in Patients with Venous Thromboembolic Disease

1992 ◽  
Vol 68 (05) ◽  
pp. 486-494 ◽  
Author(s):  
Malou Philips ◽  
Anne-Grethe Juul ◽  
Johan Selmer ◽  
Bent Lind ◽  
Sixtus Thorsen
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Normal Subjects ◽  
Tissue Type ◽  
Blood Collection ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type Plasminogen Activator ◽  
Significant Difference ◽  
Activator Inhibitor ◽  
Pai 1

SummaryA new assay for functional plasminogen activator inhibitor 1 (PAI-1) in plasma was developed. The assay is based on the quantitative conversion of PAI-1 to urokinase-type plasminogen activator (u-PA)-PAI-l complex the concentration of which is then determined by an ELISA employing monoclonal anti-PAI-1 as catching antibody and monoclonal anti-u-PA as detecting antibody. The assay exhibits high sensitivity, specificity, accuracy, and precision. The level of functional PAI-1, tissue-type plasminogen activator (t-PA) activity and t-PA-PAI-1 complex was measured in normal subjects and in patients with venous thromboembolism in a silent phase. Blood collection procedures and calibration of the respective assays were rigorously standardized. It was found that the patients had a decreased fibrinolytic capacity. This could be ascribed to high plasma levels of PAI-1. The release of t-PA during venous occlusion of an arm for 10 min expressed as the increase in t-PA + t-PA-PAI-1 complex exhibited great variation and no significant difference could be demonstrated between the patients with a thrombotic tendency and the normal subjects.

Plasminogen activator inhibitor-1 4G/5G promoter polymorphism and PAI-1 plasma levels in young patients with ischemic stroke

2011 ◽  
Vol 38 (8) ◽  
pp. 5355-5360 ◽  
Author(s):  
Adriano de Paula Sabino ◽  
Daniel Dias Ribeiro ◽  
Caroline Pereira Domingueti ◽  
Mariana Silva dos Santos ◽  
Telma Gadelha ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Young Patients ◽  
Plasminogen Activator Inhibitor ◽  
Promoter Polymorphism ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

Analysing CYP2D6*4 Allele frequency in Patients with Schizophrenia

2017 ◽  
Vol 41 (S1) ◽  
pp. S101-S102
Author(s):  
V. Djordjevic ◽  
T. Jevtovic Stoimenov
Keyword(s):  
Allele Frequency ◽  
Plasma Concentrations ◽  
Clinical Severity ◽  
Genotype Distribution ◽  
Healthy Individuals ◽  
Wild Type ◽  
Specific Pcr ◽  
Significant Difference ◽  
Schizophrenic Patients ◽  
The Right

IntroductionSchizophrenia is treated with antipsychotics and other psychotropic medications, many of which are substrates for the highly polymorphic CYP2D6 enzyme. The most frequent variant allele is CYP2D6*4- leading cause of poor metabolism (PM) phenotype. PM causes the reduction of therapeutic response, increase the risk of adverse drug reactions and increase the plasma concentration of both drug and its metabolites above the levels of toxicity.The AimAnalysing CYP2D6*4 allele frequency among schizophrenic patients for further individualisation and rationalisation of therapy.Patients and methodsResearch was conducted on 38 schizophrenic patients and 110 healthy individuals. CYP2D6*4 allele was detected with allele specific PCR.ResultsBoth wild type allele carriers are 55% of the schizophrenic patients, 45% are wild type/*4heterozygous, and *4/*4 homozygous are not identified. There is a statistically significant difference in the genotype distribution (P < 0.05) between schizophrenic patients and healthy individuals. Significantly higher *4 allele frequency (37%) comparing to healthy individuals (P < 0.0001) indicates the necessary caution in administration of CYP2D6 substrates. A lower frequency of PMs in schizophrenic patients than in healthy individuals could be explained with CYP2D6 neuroactive substrate metabolism. Forty-five percent of the schizophrenic patients are intermediate metabolisers carrying the higher risk of adverse response to CYP2D6 substrates comparing to wild type homozygous. As none of the analyzed patients was PM, exceeded plasma concentrations of medications above toxic levels are not expected when administrating the right dosage.ConclusionAltered CYP2D6 metabolism may contribute to the vulnerability, clinical severity and treatment outcome of schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Association of the CACNA2D2 gene with schizophrenia in Chinese Han population

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8521
Author(s):  
Yingli Fu ◽  
Na Zhou ◽  
Wei Bai ◽  
Yaoyao Sun ◽  
Xin Chen ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Chinese Women ◽  
Han Chinese ◽  
Type I ◽  
Genotype Distribution ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Increased Risk ◽  
Significant Difference

Background Schizophrenia (SCZ) is a severely complex psychiatric disorder in which ~80% can be explained by genetic factors. Single nucleotide polymorphisms (SNPs) in calcium channel genes are potential genetic risk factors for a spectrum of psychiatric disorders including SCZ. This study evaluated the association between SNPs in the voltage-gated calcium channel auxiliary subunit alpha2delta 2 gene (CACNA2D2) and SCZ in the Han Chinese population of Northeast China. Methods A total of 761 SCZ patients and 775 healthy controls were involved in this case-control study. Three SNPs (rs3806706, rs45536634 and rs12496815) of CACNA2D2 were genotyped by the MALDI-TOF-MS technology. Genotype distribution and allele frequency differences between cases and controls were tested by Chi-square (χ2) in males and females respectively using SPSS 24.0 software. Linkage disequilibrium and haplotype analyses were conducted using Haploview4.2. The false discovery rate correction was utilized to control for Type I error by R3.2.3. Results There was a significant difference in allele frequencies (χ2 = 9.545, Padj = 0.006) and genotype distributions (χ2 = 9.275, Padj = 0.006) of rs45536634 between female SCZ patients and female healthy controls after adjusting for multiple comparisons. Minor allele A (OR = 1.871, 95% CI [1.251–2.798]) and genotype GA + AA (OR = 1.931, 95% CI [1.259–2.963]) were associated with an increased risk of SCZ. Subjects with haplotype AG consisting of rs45536634 and rs12496815 alleles had a higher risk of SCZ (OR = 1.91, 95% CI [1.26–2.90]) compared those with other haplotypes. Conclusions This study provides evidence that CACNA2D2 polymorphisms may influence the susceptibility to SCZ in Han Chinese women.

scholarly journals Association of SHANK3 Gene Polymorphism and Parkinson Disease in the North of Iran

2021 ◽  
Vol 12 (1) ◽  
pp. 57-62
Author(s):  
Nahid Mizban ◽  
◽  
Nasim Vousooghi ◽  
Nasrin Mizban ◽  
◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Neurodegenerative Disorder ◽  
Genotype Distribution ◽  
Scaffolding Proteins ◽  
Allele Distribution ◽  
The North ◽  
Increased Risk ◽  
Significant Difference ◽  
North Of Iran ◽  
Domain 3

Introduction: Parkinson Disease (PD), the second most common chronic neurodegenerative disorder, is characterized by tremor, bradykinesia, rigidity, and postural instability. SHANK3 (SH3 and multiple ankyrin repeat domain 3) belongs to the extremely conserved ProSAP/ Shank family of synaptic scaffolding proteins. Meanwhile, rs9616915 is a non-synonymous SNP (T>C) located in the exon 6 of the SHANK3 gene, which induces substitution of isoleucine to threonine and affects the function of the resulted protein. The present study aimed to evaluate whether rs9616915 polymorphism of SHANK3 is involved in the susceptibility to PD. Methods: The study subjects were 100 patients diagnosed with PD and 100 control volunteers. The obtained samples were evaluated by the polymerase chain reaction-restriction fragment length polymorphism method. Results: A significant association was found in genotype distribution between cases and controls. Individuals with TC genotype had increased risk of PD (P=0.035, OR=1.98, 95% CI=1.04 - 3.74). No significant difference was found in allele distribution (P=0.7). Conclusion: The findings suggest that the SHANK3 rs9616915 polymorphism is associated with an increased risk of PD in the population. Further studies are needed to confirm the role of the SHANK3 gene in PD.

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