scholarly journals CDKN2A Polymorphism in Melanoma Patients in Colombian Population: A Case-Control Study

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jose D. Tovar-Parra ◽  
Luz D. Gutiérrez-Castañeda ◽  
Sebastián R. Gil-Quiñones ◽  
Jhon A. Nova ◽  
Leonardo Pulido
Keyword(s):  
Genetic Interaction ◽  
Nucleotide Polymorphisms ◽  
Chi Square ◽  
Cdkn2a Gene ◽  
Incidence And Mortality ◽  
Exon 1 ◽  
Chi Square Test ◽  
Advanced Stages ◽  
Melanoma Patients ◽  
Melanoma Subtypes

Introduction. Melanoma is the most aggressive type of skin cancer, with poor prognosis in advanced stages. The incidence and mortality rates have increased in recent years. Single nucleotide polymorphisms p.R24P, p.M53I, p.G101W, p.V126D, and p.A148T in the CDKN2A (HGNC ID: 1787) gene have been associated with the development of melanoma in different populations; however, this association has not been studied in Colombia. Methods. Cutaneous melanoma patients and healthy controls (85 cases and 166 controls) were included in this study. These subjects were screened through HRM-qPCR assay and detected variants in exon 1 and 2 of CDKN2A gene and confirmed with Sanger sequencing. Chi-square test was used to compare allele and genotype distributions between cases and controls. Odds ratio (OR) with 95% confidence interval (CI) was calculated to determine the association between polymorphisms and haplotypes with melanoma susceptibility. Statistical and haplotype analyses were performed using Stata® and R-Studio®. Results. Fifty-four percent of women were identified both in cases and controls. The frequencies of melanoma subtypes were 36,47% lentigo maligna, 24,71% acral lentiginous, 23,53% superficial extension, and 15,29% nodular. Variants in the CDKN2A gene were 11.76% in cases and 8.43% in controls. The most frequent was p.A148T in 5.88% of cases and in 4.82% of controls. GGTTG haplotype showed statistically significant differences between cases and controls ( p value = 0.04). Conclusion. CDKN2A polymorphisms p.G101W, p.R24P, p.M53I, and A148T are not associated with melanoma susceptibility in the Colombian population; further studies regarding genetic interaction and additive effects between more variants are required.

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.

Livin, a regulator of apoptosis protein, is deregulated in melanoma and serves as an independent prognostic factor—a study of 114 melanoma patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21006-21006
Author(s):  
I. Lazar
Keyword(s):  
Protein Expression ◽  
Primary Cultures ◽  
Chi Square ◽  
Apoptosis Protein ◽  
Effector Caspases ◽  
Chi Square Test ◽  
Direct Binding ◽  
Melanoma Patients ◽  
Apoptotic Activity ◽  
Second Tumor

21006 Background: Inhibitor of Apoptosis Proteins (IAP) family members inhibit apoptosis mainly by direct binding and inhibition of caspases. We previously identified the IAP Livin and demonstrated that following strong apoptotic stimuli the protein was cleaved by effector caspases to produce a truncated form with paradoxical pro-apoptotic activity. We also demonstrated that Livin is overexpressed in melanoma (M) and plays a role in chemoresistance and survival. More recently we identified synonymous single nucleotide polymorphism (SNP) in Livin at position 528(C/T) that determines expression levels of Livin protein. We found that Livin is expressed in a monoalleic manner. Normal heterozygous samples express the 528T mRNA allele and the Livin protein is not expressed. The monoallelic regulation is lost in metastatic M and the Livin protein is expressed. Methods: This study included 114 M patients that were grouped into clinical categories according to prognosis. Correlation between Livin expression and clinical parameters was examined using ANOVA, chi-square test and Kaplan-Mayer curves. Results: We found that in primary cultures from 114 M patients high, low and absence of Livin protein expression were associated with the T/C, CC and TT genotypes, respectively, at the 528(C/T) polymorphic site. Correlation of Livin expression with overall survival was significant: high expression of the Livin protein was associated with bad prognosis; survival in patients with medium expression of Livin was significantly longer compared with those without livin expression For 23 patients samples were obtained both at diagnosis and upon disease progression. All 23 first tumor sample did not express the Livin protein. Remarkably, Livin was expressed in second tumor samples from 9 of the 23 patients.and was associated with poor prognosis. Conclusions: We found that Livin expression is an independent prognosis factor in malignant M. furthermore, we describe a direct correlation between the level of Livin protein expression and survival of M patients. We also provide evidence for a novel mechanism associating synonymous SNP with control over protein expression and its deregulation during tumor progression. No significant financial relationships to disclose.

scholarly journals Complement polymorphisms and cognitive dysfunction after carotid endarterectomy

2013 ◽  
Vol 119 (3) ◽  
pp. 648-654 ◽  
Author(s):  
Eric J. Heyer ◽  
Christopher P. Kellner ◽  
Hani R. Malone ◽  
Samuel S. Bruce ◽  
Joanna L. Mergeche ◽  
...  
Keyword(s):  
Carotid Endarterectomy ◽  
Cognitive Dysfunction ◽  
Postoperative Cognitive Dysfunction ◽  
Factor H ◽  
Complement Cascade ◽  
Complement Factor ◽  
Nucleotide Polymorphisms ◽  
Chi Square ◽  
Lower Odds ◽  
Chi Square Test

Object The role of genetic polymorphisms in the neurological outcome of patients after carotid endarterectomy (CEA) remains unclear. There are single nucleotide polymorphisms (SNPs) that predispose patients to postoperative cognitive dysfunction (CD). We aim to assess the predictability of three complement cascade-related SNPs for CD in patients having CEAs. Methods In 252 patients undergoing CEA, genotyping was performed for the following polymorphisms: complement component 5 (C5) rs17611, mannose-binding lectin 2 (MBL2) rs7096206, and complement factor H (CFH) rs1061170. Differences among genotypes were analyzed via the chi-square test. Patients were evaluated with a neuropsychometric battery for CD 1 day and 1 month after CEA. A multiple logistic regression model was created. All variables with univariate p < 0.20 were included in the final model. Results The C5 genotypes A/G (OR 0.26, 95% CI 0.11–0.60, p = 0.002) and G/G (OR 0.22, 95% CI 0.09–0.52, p < 0.001) were significantly associated with lower odds of exhibiting CD at 1 day after CEA compared with A/A. The CFH genotypes C/T (OR 3.37, 95% CI 1.69–6.92, p < 0.001) and C/C (OR 3.67, 95% CI 1.30–10.06, p = 0.012) were significantly associated with higher odds of exhibiting CD at 1 day after CEA compared with T/T. Statin use was also significantly associated with lower odds of exhibiting CD at 1 day after CEA (OR 0.43, 95% CI 0.22–0.84, p = 0.01). No SNPs were significantly associated with CD at 1 month after CEA. Conclusions The presence of a deleterious allele in the C5 and CFH SNPs may predispose patients to exhibit CD after CEA. This finding supports previous data demonstrating that the complement cascade system may play an important role in the development of CD. These findings warrant further investigation.

scholarly journals Zinc transporter-3 [SLC30A3 (rs11126936)] polymorphism is associated with major depressive disorder in Asian subjects

2019 ◽  
Vol 2 (3) ◽  
pp. 20-28 ◽  
Author(s):  
Munn Sann Lye ◽  
Aishah-Farhana Shahbudin ◽  
Yin Yee Tey ◽  
Yin Sim Tor ◽  
King Hwa Ling ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Conditional Logistic Regression ◽  
Zinc Transporter ◽  
Polymorphism Analysis ◽  
Nucleotide Polymorphisms ◽  
Major Depressive ◽  
Chi Square ◽  
Increased Risk ◽  
Chi Square Test

Major depressive disorder (MDD) compromises the individual’s capacity for self-care and productivity. Single nucleotide polymorphisms (SNP) of a number of genes have been associated with MDD. The zinc transporter-3 protein, encoded by the ZnT3 (SLC30A3) gene, maintains zinc-glutamate homeostasis at the glutamatergic synapse, a disruption of which increases risk of MDD. We hypothesise that variation in SLC30A3 (rs11126936) SNP increases risk of MDD. We recruited 300 MDD cases and 300 controls, matched in the ratio of 1:1 by age, gender and ethnicity. PCR-restriction fragment length polymorphism analysis was used in DNA genotyping, validated by sequencing 10% of samples. Deviation from the Hardy-Weinberg equilibrium was tested using the chi-square test. Conditional logistic regression was used to estimate adjusted odds ratios, controlling for age, gender, ethnicity, occupation and family monthly income. Genotypes G/G and G/T showed two times greater odds of developing MDD compared to variant genotype T/T (OR=1.983, 95% CI=1.031-3.815; p=0.040 and OR=2.232, 95% CI=1.100-4.533; p=0.026 respectively). Carriers of genotypes G/G and G/T of the SNP rs11126936 in SLC30A3 are associated with increased risk of MDD.

scholarly journals Periodontitis Is Associated With Risk of Conventional Stent Restenosis: Pilot Case-Control Study

2021 ◽  
Vol 2 ◽  
Author(s):  
Raphael Osugue ◽  
Nidia C. Castro dos Santos ◽  
Cassia F. Araujo ◽  
Flavio X. de Almeida ◽  
Magda Feres ◽  
...  
Keyword(s):  
Coronary Angioplasty ◽  
Alveolar Bone ◽  
Stepwise Logistic Regression ◽  
Tissue Destruction ◽  
Chi Square ◽  
Percutaneous Coronary Angioplasty ◽  
Stent Restenosis ◽  
Chi Square Test ◽  
Advanced Stages ◽  
And Control

Objectives: Percutaneous coronary angioplasty with stent implantation has been established as the main form of treatment of atherosclerosis. However, 16 to 44% of patients may evolve with stent restenosis. Periodontitis is an inflammatory condition associated with bacterial infection, that may lead to periodontal tissue destruction and tooth loss. This study aimed to evaluate the association between stent restenosis and periodontitis.Materials and Methods: Coronary angiography exams presenting stent imaging with and without restenosis were analyzed. Patients meeting the inclusion and exclusion criteria were selected and allocated in 2 groups: case (restenosis) and control (without restenosis). We evaluated if systemic and periodontal variables were predictors of restenosis (primary outcome) using a multivariable stepwise logistic regression. Additionally, we compared clinical and periodontal conditions between the control and case groups (secondary outcomes) using Chi-square test and ANOVA test.Results: Data from 49 patients (case n = 15; control n = 34) were analyzed. The results showed that stages III and IV periodontitis and lack of physical activity were significant predictors of stent restenosis (OR 5.82 and 5.98, respectively). Comparisons regarding the diagnosis of periodontal conditions between control and case groups did not present significant differences in the incidence of periodontitis and alveolar bone loss.Conclusion: Stages III and IV periodontitis increased the incidence of stent restenosis. These findings suggest that advanced stages of periodontal disease might lead to the occurrence of negative outcomes after coronary angioplasty with stent placement.

FXII (46C→T) Polymorphism and In Vivo Generation of FXII Activity

1999 ◽  
Vol 81 (05) ◽  
pp. 745-747 ◽  
Author(s):  
H. P. Kohler ◽  
T. S. Futers ◽  
P. J. Grant
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Point Mutation ◽  
Suspected Coronary Artery Disease ◽  
Factor Xii ◽  
Chi Square ◽  
Exon 1 ◽  
Chi Square Test ◽  
Artery Disease

SummaryIncreased Factor XIIa concentrations have been found in association with coronary artery disease. Recently, a common 46 C to T point mutation in exon 1 of the factor XII gene has been described which is associated with lower FXII clotting activity and lower zymogen levels in relation to possession of the T allele. It is not known whether this polymorphism relates to the phenotypes of FXIIa in vivo or to coronary artery disease. The aim of the study was to investigate the interaction of this polymorphism with FXIIa plasma levels and to study the prevalence of the polymorphism in 266 patients with suspected coronary artery disease characterised by angiography and in 185 healthy controls. FXIIa levels were strongly associated with FXII genotype with lower levels with increasing numbers of T alleles (p <0.0001). There was no difference between the prevalence of this polymorphism in patients with MI compared to those without MI and controls and between all patients and controls (p ≥0.2, chi-square test). There was no association between extent of coronary artery disease (0, 1, 2, and 3 vessel disease) and FXII genotype. In conclusion, the common 46 C to T point mutation is strongly associated with FXIIa but the present study did not show an association with coronary artery disease. The role of this polymorphism in other thrombotic disorders such as ischemic stroke and venous thrombosis and its clinical significance in FXII deficient states remains to be investigated.

ABCB1, CYP3A5*3, and CYP3A4*1B SNPs and risk of toxicity with sunitinib treatment for mRCC.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 485-485
Author(s):  
Maria Bassanelli ◽  
Alessandra Felici ◽  
Michele Milella ◽  
Diana Giannarelli ◽  
Silvana Giacinti ◽  
...  
Keyword(s):  
Nucleotide Polymorphisms ◽  
Test Results ◽  
Chi Square ◽  
Metabolizing Enzymes ◽  
Single Nucleotide ◽  
Genes Encoding ◽  
Hand Foot Syndrome ◽  
Chi Square Test ◽  
Grade 3 ◽  
The Individual

485 Background: Currently there are no biomarkers to predict either toxicity or activity of targeted therapy in mRCC. The aim of this study was to correlate single nucleotide polymorphisms (SNPs) of genes encoding for efflux transporters and metabolizing enzymes with sunitinib toxicity in metastatic renal cell carcinoma (mRCC) patients (pts). Methods: We conducted an observational, retrospective analysis of 60 Caucasian pts who received sunitinib for mRCC from 2 Italian institutions. Correlation between adverse events (AE, according to CTCAE v.4.0) and 4 polymorphisms in 3 genes (ABCB1 [1236C>T, 3435C>T], CYP3A5*3 6986A>G, CYP3A4*1B-392A>G) was analyzed. SNPs were detected in blood samples using pyrosequencing technique. Association between SNPs and toxicities was evaluated using the Chi Square test. Results: 60pts (median age: 61 years; male: 63.3%) with mRCC (clear cell: 85%, other histologies: 15%) were treated with sunitinib (83.3% as first-line). The most common AE (any-grade) reported were: hypertension (85%), asthenia (83.3%), hypothyroidism (65%), anemia (61.6%), nausea/vomiting (60%), stomatitis (58.3%), diarrhoea (48.3%), neutropenia (48.3%), thrombocytopenia (46.7%), leukopenia (46.7%), hypertriglyceridemia (45%), hyperglycaemia (38.4%), hypercholesterolemia (35%), and hand-foot syndrome (35%). Treatment was discontinued and sunitinib dose was reduced due to AE in 28.3% and 61.7% of pts, respectively. The G/A-variant in CYP3A5*3 was associated with thrombocytopenia (any grade, p=0.03); homozygous C/C alleles in ABCB1 1236C>T significantly correlated with leukopenia (any grade, p=0.01), while the C/C genotype in ABCB1 3435C>T was associated with hypertension (grade≥3, p=0.05); hypertriglyceridemia showed a trend towards increased prevalence in the presence of the C allele (grade≥3, p=0.08). Conclusions: Polymorphisms in ABCB1 and CYP3A5*3 are predictive of toxicity, as hypertension, leukopenia, and thrombocytopenia in pts with mRCC treated with sunitinib. This analysis could support the selection of the more appropriate drug to the individual patient.

Expression of CD44 and CD133 in tumor сells of metastatic and non-metastatic gastric cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15531-e15531
Author(s):  
Aleksandr B. Sagakyants ◽  
Oleg I. Kit ◽  
Elena P. Ulianova ◽  
Elena Yu. Zlatnik ◽  
Inna A. Novikova ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immunohistochemical Study ◽  
Single Cells ◽  
Chi Square ◽  
Positive Expression ◽  
Tumor Tissues ◽  
Incidence And Mortality ◽  
Chi Square Test ◽  
Group 2 ◽  
Group 1

e15531 Background: High incidence and mortality rates of gastric cancer cause a constant search for the most informative and effective methods of diagnosis and treatment assessment. In this regard, studying the expression of markers with the stem phenotype in primary tumor tissues in patients with gastric cancer with and without metastases is of undoubted interest. Methods: The study included 20 gastric cancer patients aged 30-80 years: group 1 – gastric cancer T3-4аN0-3M0 (G2) without metastasis (58.9±9.7 years); group 2 – gastric cancer T3-4аN0-3M1 (G2) with peritoneal metastasis (53.4±11.9 years). Immunohistochemical study was performed on paraffin-embedded tumor tissue sections using mouse monoclonal antibodies to CD44 (156-3С11 Thermo Scientific) at a 1:2500 dilution and rabbit polyclonal antibodies to CD133 (Cloud-Clone Corp.) at a 1:700 dilution; the Thermo Scientific autostainer was used for staining. Membrane staining and staining intensity were assessed: 0, 1+ weak, 2+ moderate, 3+ strong staining. Positive expression was defined as ≥10% cut-off for CD44 and ˃5% for CD133. Results: Positive expression of CD44+ was detected in 67% (13) in group 2 vs. 20% (4) in group 1. In the metastatic group, the number of cells that stained positive for CD44 expression ranged from 9 to 15%, on average 10.0±3.08%, without metastases – from single cells to 13%, on average 6.0±2.3%. A chi-square test showed statistically significant association in the groups (8.256 at p = 0.004). Positive CD133+ expression in tumor tissues was registered in 100% (20) in group 2 and 80% (16) in group 1. The range of positively stained cells in group 2 was from 10 to 40%, on average 21.3±11.6%, in group 1 - from single cells to 14%, on average 10.0±2.4%. A chi-square test showed statistically significant association in the groups (4.444 at p = 0.036). Conclusions: Immunohistochemical study of the selected tumor cell markers in gastric cancer revealed some characteristics of their expression depending on the presence of metastases. The results can be the basis for further research for the most complete characterization of a heterogeneous tumor population in gastric cancer and the role of individual cells in the tumor growth, progression and metastasis.

scholarly journals The influence of CYP1A1 and CYP1A2 polymorphisms on stroke risk in the Chinese population

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Yan Mao ◽  
Lin Yang ◽  
Qian Chen ◽  
Guoqing Li ◽  
Yao Sun ◽  
...  
Keyword(s):  
Lower Risk ◽  
Chinese Population ◽  
Stroke Risk ◽  
Nucleotide Polymorphisms ◽  
Chi Square ◽  
Gender Stratification ◽  
Chi Square Test ◽  
Traditional Risk Factors ◽  
The Relationship ◽  
Cerebral Blood Circulation

Abstract Backgrounds Stroke is a sudden disorder of cerebral blood circulation. Many studies have illustrated that dyslipidemia, hypertension, diabetes, smoking and excessive drinking are the traditional risk factors for stroke. This study aimed to observe the relationship between CYP1A1 and CYP1A2 variants and stroke risk in the Chinese population. Methods Agena MassARRAY Assay was used to genotype four single nucleotide polymorphisms (SNPs) in 477 cases and 480 controls. The chi-square test and logistic-regression analysis were used to explore the relationship between CYP1A1 and CYP1A2 variants and stroke risk. Results Individuals with CYP1A2 rs762551 C was associated with a lower risk of stroke than that of allele A. Age stratification analysis showed that rs762551 was only observed to be associated with a lower risk of stroke in ≤64ys age group. After gender stratification analysis, a significant association between rs762551 and stroke risk was found in males, but not in females. The four SNPs were found to be correlated with stroke risk in patients with hypertension, coronary heart disease, cerebral infarction and lacunar infarction. Conclusion In this study, the results first showed that CYP1A1 and CYP1A2 variants were associated with stroke risk. Larger and well-designed studies are needed to confirm the results.

scholarly journals Genetic variations in methotrexate metabolic pathway genes influence methotrexate responses in rheumatoid arthritis patients in Malaysia

2021 ◽  
Author(s):  
Hong Xi Sha ◽  
Kumar Veerapen ◽  
Sook Khuan Chow ◽  
Suk Chyn Gun ◽  
Ing Soo Lau ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Binary Logistic Regression ◽  
Nucleotide Polymorphisms ◽  
Chi Square ◽  
Single Nucleotide ◽  
Therapeutic Outcomes ◽  
Gene Environment ◽  
Chi Square Test ◽  
Toxicity Analysis ◽  
Rheumatic Drug

Abstract Methotrexate (MTX) is the most widely used disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA). Many studies have attempted to understand the genetic risk factors that affect the therapeutic outcomes in RA patients treated with MTX. Unlike other studies that focus on the populations of Caucasians, Indian and east Asian countries, this study investigated the impacts of six single nucleotide polymorphisms (SNPs) that are hypothesized to affect the outcomes of MTX treatment in Malaysian RA patients. A total of 647 RA patients from three ethnicities (NMalay = 153; NChinese = 326; NIndian = 168) who received MTX monotherapy (minimum 15 mg per week) were sampled from three hospitals in Malaysia. SNPs were genotyped in patients using TaqMan real-time PCR assay. Data obtained were statistically analysed for the association between SNPs and MTX efficacy and toxicity. Analysis of all 647 RA patients indicated that none of the SNPs has influence on either MTX efficacy or MTX toxicity according to the Chi-square test and binary logistic regression. However, stratification by self-identified ancestries revealed that two out of six SNPs, ATIC C347G (rs2372536) (OR=0.5478, 95%CI=0.3396-0.8835, p=0.01321) and ATIC T675C (rs4673993) (OR=0.5247, 95%CI=0.3248-0.8478, p=0.008111), were significantly associated with MTX adequate response in RA patients with Malay ancestry (p < 0.05). As for the MTX toxicity, no significant association was identified for any SNPs selected in this study. Taken all together, ATIC C347G and ATIC T675C can be further evaluated on their impact in MTX efficacy using larger ancestry-specific cohort, and also incorporating high-order gene-gene and gene-environment interactions.

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