Genetic variations in tumor necrosis factor related apoptosis-inducing ligand receptor-1 (TRAIL-R1) gene and the susceptibility to B cell nonhodgkin lymphoma in Egypt

2021 ◽  
pp. 1-8
Author(s):  
Mervat Khorshied ◽  
Nohair Soliman ◽  
Ola Khorshid ◽  
Salwa Bakr
Keyword(s):  
Large Scale ◽  
Genetic Variations ◽  
Nucleotide Polymorphisms ◽  
Apoptotic Pathway ◽  
Increased Risk ◽  
Genotypic Analysis ◽  
Large Scale Dataset ◽  
R1 Gene ◽  
And Gender ◽  
Nonhodgkin Lymphoma

BACKGROUND: Dysregulated apoptosis is a hallmark of cancer development and progression. TRAIL and its receptors (R1 and R2) are key players in the extrinsic apoptotic pathway. Genetic alteration or blockade of TRAIL-R1 may alter its apoptotic function, and subsequently provide growth advantage to neoplastic cells. OBJECTIVE: to investigate the possible association between -C626G, -A683C and -A1322G single nucleotide polymorphisms (SNPs) of TRAIL-R1 gene and the susceptibility to B-NHL in a cohort of Egyptians. METHODS: Genotypic analysis was performed for 100 newly diagnosed B-NHL patients and 150 age and gender matched healthy controls. RESULTS: The polymorphic alleles of -C626G and -A1322G conferred almost twofold increased risk of B-NHL (OR = 1.76; 95%CI = 1.01–3.22 and OR = 1.89; 95%CI = 1.01–3.75 respectively). There was no statistical difference in the distribution of TRAIL-R1-A683C alleles/genotypes between B-NHL patients and controls. B-NHL risk increased when -C626G and -A1322G polymorphic genotypes were co-inherited (OR = 3.57; 95%CI = 1.29–9.84). The risk conferred by -C626G SNP increased for DLBCL (OR = 3.39, 95% CI: 1.61–7.16). CONCLUSION: TRAIL-R1–C626G and -A1322G polymorphisms could be considered as molecular risk factors for B-NHL especially DLBCL. The data provided by the current study constitute an initial millstone towards developing a large-scale dataset for genetic variations that could contribute to lymphomagenesis in Egyptian population.

scholarly journals LINC01414/LINC00824 genetic polymorphisms in association with the susceptibility of chronic obstructive pulmonary disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoman Zhou ◽  
Yunjun Zhang ◽  
Yutian Zhang ◽  
Quanni Li ◽  
Mei Lin ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Genetic Polymorphisms ◽  
Chronic Obstructive ◽  
Nucleotide Polymorphisms ◽  
Obstructive Pulmonary Disease ◽  
Logistic Analysis ◽  
Copd Patients ◽  
Increased Risk ◽  
And Gender

Abstract Objective Chronic obstructive pulmonary disease (COPD) is a complicated multi-factor, multi-gene disease. Here, we aimed to assess the association of genetic polymorphisms in LINC01414/ LINC00824 and interactions with COPD susceptibility. Methods Three single nucleotide polymorphisms (SNPs) in LINC01414/LINC00824 was genotyped by Agena MassARRAY platform among 315 COPD patients and 314 controls. Logistic analysis adjusted by age and gender were applied to estimate the genetic contribution of selected SNPs to COPD susceptibility. Results LINC01414 rs699467 (OR = 0.73, 95% CI 0.56–0.94, p = 0.015) and LINC00824 rs7815944 (OR = 0.56, 95% CI 0.31–0.99, p = 0.046) might be protective factors for COPD occurrence, while LINC01414 rs298207 (OR = 2.88, 95% CI 1.31–6.31, p = 0.008) risk-allele was related to the increased risk of COPD in the whole population. Rs7815944 was associated with the reduced risk of COPD in the subjects aged > 70 years (OR = 0.29, p = 0.005). Rs6994670 (OR = 0.57, p = 0.007) contribute to a reduced COPD risk, while rs298207 (OR = 7.94, p = 0.009) was related to a higher susceptibility to COPD at age ≤ 70 years. Rs298207 (OR = 2.54, p = 0.043) and rs7815944 (OR = 0.43, p = 0.028) variants was associated COPD risk among males. Rs7815944 (OR = 0.16, p = 0.031) was related to the reduced susceptibility of COPD in former smokers. Moreover, the association between rs298207 genotype and COPD patients with dyspnea was found (OR = 0.50, p = 0.016), and rs7815944 was related to COPD patients with wheezing (OR = 0.22, p = 0.008). Conclusion Our finding provided further insights into LINC01414/LINC00824 polymorphisms at risk of COPD occurrence and accumulated evidence for the genetic susceptibility of COPD.

scholarly journals Genetic Variations in the PI3K/PTEN/AKT/mTOR Pathway Are Associated With Clinical Outcomes in Esophageal Cancer Patients Treated With Chemoradiotherapy

2009 ◽  
Vol 27 (6) ◽  
pp. 857-871 ◽  
Author(s):  
Michelle A.T. Hildebrandt ◽  
Hushan Yang ◽  
Mien-Chie Hung ◽  
Julie G. Izzo ◽  
Maosheng Huang ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Genetic Variations ◽  
Chemotherapeutic Agents ◽  
Response To Therapy ◽  
Nucleotide Polymorphisms ◽  
Chemotherapeutic Regimen ◽  
Risk Of Death ◽  
Increased Risk

Purpose The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. Patients and Methods Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. Results We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes—AKT2 and FRAP1—were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). Conclusion These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen.

scholarly journals Single nucleotide polymorphisms associated with gastric cancer in Iranian patients

2021 ◽  
Vol 7 (2) ◽  
pp. e37-e37
Author(s):  
Arash Alghasi ◽  
Gholamreza Farnoosh ◽  
Ali Saeedi Boroujeni ◽  
Mohammad Bahadoram ◽  
Sima Tahmaseby Gandomkari ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Large Scale ◽  
Nucleotide Polymorphisms ◽  
Caspase 9 ◽  
Northern Iran ◽  
Single Nucleotide ◽  
C677t Mthfr ◽  
Increased Risk ◽  
Iranian Patients

Gastric cancer is one of the leading worldwide cancers formed in the lining of the stomach, and is the most prevalent cancer in northern Iran. Recent interventions for the early diagnosis of gastric cancer are based on genetic susceptibility parameters and the interactions between genes and the environment. Accordingly, this narrative review was designed to summarize the genetic markers involved in Iranian patients with gastric cancer, classified by cellular function. There was a significant relationship between single nucleotide polymorphisms (SNPs) in rs1051208 C allele (RAF1), rs531564 (pri-miR-124-1), rs1053023 (STAT3), rs8193 C allele (CD44), rs3130932G allele (OCT4), rs283821943, rs2032586 (ABCB1), codons 72,248 (p53), -137 G/C (IL-18), Pro12Ala (PPARγ), rs1053023 (STAT3), rs4647603 (caspase 3), -712C>T (caspase 9), -1263 A> (caspase 9) and gastric cancer. Increased risk was observed in C677T (MTHFR). Finally, decreased risk of gastric cancer was explored in -938 C>A (bcl2). Asp299Gly (TLR-4), rs1028181-513T/C (IL-19) Pro12Ala (PPARγ) may play a crucial role in susceptibility of Helicobacter pylori and gastric pathogenesis. According to the findings, the genetic polymorphisms in the immune-associated genes were related to the gastric cancer among the Iranian patients. Therefore, further large-scale functional investigations are needed to draw definite conclusions.

scholarly journals A brief overview of GWAS: discover genetic variations of diseases and phenotypes

2020 ◽  
Vol 185 ◽  
pp. 03014
Author(s):  
Zhiying Peng
Keyword(s):  
Large Scale ◽  
Genome Wide Association Study ◽  
Genetic Variations ◽  
Nucleotide Polymorphisms ◽  
Information Discovery ◽  
Genome Wide ◽  
Whole Genomes ◽  
Statistical Analysis Method ◽  
History Of ◽  
Application Fields

GWAS, or Genome-wide association study, is a statistical analysis method to reveal specific genetic variations, usually single nucleotide polymorphisms, with particular phenotypes or diseases. The power to scan whole genomes from large scale samples made the method an efficient tool for information discovery. In the last decades, the application of GWAS has flourished, which benefited our understanding related to diseases, breeding and many other topics. In this review, we overviewed the history of GWAS, as well as different approaches to perform the analysis under different circumstances during different stages. Meanwhile, we also showed how different GWAS approaches benefited diverse research and application fields, and the potential limitations of the method.

scholarly journals Associations between Aquaglyceroporin Gene Polymorphisms and Risk of Type 2 Diabetes Mellitus

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yijun Wang ◽  
Gang Chen ◽  
Qingyun Tu ◽  
Junxia Wu ◽  
Yu Qin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Diseases ◽  
Proteinase K ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Polymerase Chain ◽  
And Gender

Objectives. AQP7 and AQP9 represent glycerol channel in adipose tissue and liver and have been associated with metabolic diseases. We aimed to investigate the associations between genetic variants in AQP7 and AQP9 genes and the risk of type 2 diabetes (T2DM) in Chinese population. Methods. Blood samples were drawn from 400 T2DM patients and 400 age- and gender-matched controls. Genomic DNA was extracted by proteinase K digestion and phenol–chloroform extraction. Genotyping of 5 single nucleotide polymorphisms (SNPs) in AQP7 (rs2989924, rs3758269, and rs62542743) and AQP9 (rs57139208, rs16939881) was performed by the polymerase chain reaction assay with TaqMan probes. Results. The subjects with rs2989924 GA+AA genotypes had 1.47-fold increased risk of T2DM (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.06-2.04), compared to those with GG genotype, and this association remained significant after adjustment for covariates (OR 1.66, 95% CI 1.07-2.57). When compared with rs3758269 CC genotype, the subjects with CT+TT genotypes had 45% decreased T2DM risk after multivariate adjustment (OR 0.55, 95% CI 0.35-0.85). The associations were evident in elder and overweight subjects and those with central obesity. No association was observed between AQP9 SNPs and T2DM risk. Conclusions. AQP7 SNP rs2989924 and rs3758269 were associated with T2DM risk in Chinese Han population.

Interactive Effects of a Combination of the HDAC3 and HDAC9 Genes with Diabetes Mellitus on the Risk of Ischemic Stroke

2020 ◽  
Author(s):  
Hung-Yi Chiou ◽  
Chyi-Huey Bai ◽  
Li-Ming Lien ◽  
Chaur-Jong Hu ◽  
Jiann-Shing Jeng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Ischemic Stroke ◽  
Interactive Effect ◽  
Interactive Effects ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Plaque Score ◽  
Polygenic Score ◽  
Increased Risk ◽  
And Gender

Abstract Background and Aim Previous studies indicated that the HDAC3 and HDAC9 genes play critical roles in atherosclerosis and ischemic stroke (IS). The purpose of this study was to investigate the association of combined single-nucleotide polymorphisms in the HDAC3 and HDAC9 genes with the susceptibility to IS. Methods A case–control study was conducted including 863 IS patients and 863 age- and gender-matched healthy participants. A polygenic score was developed to estimate the contribution of a combination of the HDAC3 and HDAC9 genes to the risk of IS. The interactive effects of traditional risk factors of stroke and the polygenic score on the risk of IS were explored. Additionally, the association between the polygenic score and the progression of atherosclerosis, a potential risk factor of IS, was examined in our healthy controls. Results Subjects with a higher polygenic score had an increased risk of IS (odds ratio: 1.83; 95% confidence interval: 1.38–2.43) after adjusting for covariates compared with individuals with a lower polygenic score. An interactive effect of diabetes mellitus and the polygenic score on the risk of IS was observed. A significant positive correlation between the polygenic score and a change in the plaque score (standardized β = 0.42, p = 0.0235) in healthy controls with diabetes mellitus was found. Conclusion Our results suggested that the combination of the HDAC3 and HDAC9 genes with a history of diabetes mellitus could exacerbate the deterioration of atherosclerosis, thereby increasing the risk of IS. Further studies are warranted to explore our results in other populations.

scholarly journals Haplotypes of HTRA1 rs1120638, TIMP3 rs9621532, VEGFA rs833068, CFI rs10033900, ERCC6 rs3793784, and KCTD10 rs56209061 Gene Polymorphisms in Age-Related Macular Degeneration

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Rasa Liutkeviciene ◽  
Alvita Vilkeviciute ◽  
Greta Gedvilaite ◽  
Kriste Kaikaryte ◽  
Loresa Kriauciuniene
Keyword(s):  
Macular Degeneration ◽  
Protective Factor ◽  
Protective Role ◽  
Age Related Macular Degeneration ◽  
Nucleotide Polymorphisms ◽  
Exudative Amd ◽  
Age Related ◽  
Increased Risk ◽  
And Gender ◽  
The Impact

Background. To determine the impact of HTRA1 rs1120638, TIMP3 rs9621532, VEGFA rs833068, CFI rs10033900, ERCC6 rs3793784, and KCTD10 rs56209061 genotypes on the development of age-related macular degeneration (AMD) in the Lithuanian population. Methods. A total of 916 subjects were examined: 309 patients with early AMD, 301 patients with exudative AMD, and 306 healthy controls. The genotyping of HTRA1 rs11200638, TIMP3 rs9621532, VEGFA rs833068, CFI rs10033900, ERCC6 rs3793784, and KCTD10 rs56209061 was carried out using the RT-PCR method. Results. Our study showed that single-nucleotide polymorphisms rs3793784 and rs11200638 were associated with increased odds of early and exudative AMD, and the variant in KCTD10 (rs56209061) was found to be associated with decreased odds of early and exudative AMD development after adjustments for age and gender in early AMD analysis and after adjustments only for age in exudative AMD. The haplotype containing two minor alleles C-A and the G-A haplotype in rs3793784-rs11200638 were statistically significantly associated with an increased risk of exudative AMD development after adjustment for age, while the G-G haplotype showed a protective role against early and exudative AMD and the haplotype C-G in rs3793784-rs11200638 was associated with a decreased risk only of exudative AMD development. Conclusions. Our study identified two markers, rs11200638 and rs3793784, as risk factors for early and exudative AMD, and one marker, rs56209061, as a protective factor for early and exudative AMD development. The haplotypes constructed of rs3793784-rs11200638 were found to be associated with AMD development, as well.

scholarly journals ABCC2(rs717620), and ABCC3 (rs4793665) affect high dose Methotrexate toxicity, and outcome in children with osteosarcoma

2020 ◽  
Author(s):  
Amr Yahia ◽  
Rania Labib ◽  
Sameh A. Abdelshafi3 ◽  
Asmaa Salama ◽  
Omneya Hassanain ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Plasma Concentrations ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Nucleotide Polymorphisms ◽  
Dose Methotrexate ◽  
Increased Risk ◽  
Patients At Risk ◽  
And Gender ◽  
Age Range

Objectives: Osteosarcoma (OS) is one of the aggressive bone tumors commonly diagnosed in adolescents and young adults. The study investigated the effect of 9 single nucleotide polymorphisms (SNPs) in 5 genes on methotrexate (MTX) plasma level and its impact on the patients’ clinical outcomes. Methods: One hundred and thirty-three patients with OS (68 boys and 65 girls with age range 4.00-17.86 years) were enrolled and treated with four weeks of high-dose methotrexate (HDMTX) as neo-adjuvant therapy in children’s cancer hospital (CCHE-57357). Blood samples were collected and genotyped for the studied SNPs (MTHFR rs1801133, SLCO1B1 rs11045879, rs4149081, rs2306283, ABCC3 rs4793665, rs4148412, rs733392 ABCG2 rs2231142, and ABCC2 rs717620 using Taqman® (RT-PCR) assay. Plasma concentrations of MTX were measured using the enzyme multiple immunoassay technique (EMIT®). The clinical outcomes included toxicities that were evaluated based on the common terminology criteria for adverse events - version 5 (CTCAEv5.0.), besides the studying of survival analysis and tumor necrosis (TN %). Results: Older patients experienced increased risk of delayed MTX elimination at 72-hour, OR=1.19 (95% CI=1.09-1.29, p=0.00059). The studied SNPs weren’t associated with MTX elimination. Patients with ABCC2 HW (Homozygous wild) genotype group showed a high statistically significant association with higher grade hyperbilirubinemia, OR= 2.05(95% CI=1.05-4.01, p=0.037). Moreover, the patients with ABCC3 (rs4793665) HV and HT (Homozygous variant and Heterozygous) genotypes had a significant association with severe nephrotoxicity, OR= 0.34(95% CI=1.6-0.72, p=0.005). Conclusions: ABCC2 (rs717620), ABCC3 (rs4793665) genotyping with age and gender could help in predicting patients at risk of toxicities due to HDMTX.

Role of CD24 Polymorphisms in the Susceptibility to Inflammatory Bowel Disease

2014 ◽  
Vol 29 (1) ◽  
pp. e62-e68 ◽  
Author(s):  
Victoria Lisiansky ◽  
Sarah Kraus ◽  
Inna Naumov ◽  
Dina Kazanov ◽  
Ilana Nabiochtchikov ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Rflp Analysis ◽  
Restriction Enzymes ◽  
Nucleotide Polymorphisms ◽  
Logistic Regression Models ◽  
Younger Age ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
And Gender

Background Inflammatory bowel disease (IBD) results from an inappropriate inflammatory response in which genetic, immune, and environmental factors all play important roles. Recently, single nucleotide polymorphisms (SNPs) in the CD24 gene have been associated with the development of several autoimmune diseases. Aim To evaluate whether CD24 SNPs, are associated with risk of ulcerative colitis (UC) and Crohn's disease (CD). Methods The CD24 polymorphisms C170T (rs8734), TG1527del (rs3838646), A1626G (rs1058881), and A1056G (rs1058818) were assessed in a case-control study of an Israeli cohort comprising 117 IBD patients and 105 age and gender-matched healthy controls. Restriction fragment length polymorphism (RFLP) analysis was performed using BstX1, Bsr1, Mfe1, and BstU1 restriction enzymes. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression models. Results Carriers of the C170T SNP were at increased risk of IBD (OR=3.022, 95% CI: 1.748–5.223, p=0.001), UC (OR=3.002, 95% CI: 1.661–5.427, p=0.001) and CD (OR=3.077, 95% CI: 1.334–7.095, p=0.008). Carrying the A1626G and A1056G SNPs was found to be a risk factor for IBD (OR=2.460, 95% CI: 1.420–4.259, p=0.001 and OR=1.856, 95% CI: 1.011–3.405, p=0.01), UC (OR=2.218, 95% CI: 1.207–4.075, p=0.01 and OR=1.944, 95% CI: 0.995–3.798, p=0.01) but not for CD (p=0.086 and p=0.299). The A1626G and TG1527del were found to be associated with younger age of IBD onset (p=0.022 and p=0.027, respectively). Conclusions The CD24 C170T polymorphism is associated with IBD risk. The A1626G and A1056G SNPs might be associated only with UC risk. These findings suggest CD24 as a new genetic susceptibility factor, with clinical implications in the prediction of IBD prognosis and therapy.

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