scholarly journals Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 808
Author(s):  
Laura Pérez-Lago ◽  
Teresa Aldámiz-Echevarría ◽  
Rita García-Martínez ◽  
Leire Pérez-Latorre ◽  
Marta Herranz ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Evolutionary Dynamics ◽  
Viral Evolution ◽  
Special Focus ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
New Variant ◽  
History Of ◽  
Evolution Dynamics ◽  
The Uk

A successful Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant, B.1.1.7, has recently been reported in the UK, causing global alarm. Most likely, the new variant emerged in a persistently infected patient, justifying a special focus on these cases. Our aim in this study was to explore certain clinical profiles involving severe immunosuppression that may help explain the prolonged persistence of viable viruses. We present three severely immunosuppressed cases (A, B, and C) with a history of lymphoma and prolonged SARS-CoV-2 shedding (2, 4, and 6 months), two of whom finally died. Whole-genome sequencing of 9 and 10 specimens from Cases A and B revealed extensive within-patient acquisition of diversity, 12 and 28 new single nucleotide polymorphisms, respectively, which suggests ongoing SARS-CoV-2 replication. This diversity was not observed for Case C after analysing 5 sequential nasopharyngeal specimens and one plasma specimen, and was only observed in one bronchoaspirate specimen, although viral viability was still considered based on constant low Ct values throughout the disease and recovery of the virus in cell cultures. The acquired viral diversity in Cases A and B followed different dynamics. For Case A, new single nucleotide polymorphisms were quickly fixed (13–15 days) after emerging as minority variants, while for Case B, higher diversity was observed at a slower emergence: fixation pace (1–2 months). Slower SARS-CoV-2 evolutionary pace was observed for Case A following the administration of hyperimmune plasma. This work adds knowledge on SARS-CoV-2 prolonged shedding in severely immunocompromised patients and demonstrates viral viability, noteworthy acquired intra-patient diversity, and different SARS-CoV-2 evolutionary dynamics in persistent cases.

Short Communication: Does Interleukin-28B Single Nucleotide Polymorphisms Influence the Natural History of Hepatitis B?

2012 ◽  
Vol 28 (10) ◽  
pp. 1262-1264 ◽  
Author(s):  
Luz Martín-Carbonero ◽  
Norma I. Rallón ◽  
José M. Benito ◽  
Eva Poveda ◽  
Juan González-Lahoz ◽  
...  
Keyword(s):  
Natural History ◽  
Hepatitis B ◽  
Single Nucleotide Polymorphisms ◽  
Short Communication ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Interleukin 28B ◽  
History Of

Differentiation between wild-type and vaccines strains of varicella zoster virus (VZV) based on four single nucleotide polymorphisms

2017 ◽  
Vol 145 (12) ◽  
pp. 2618-2625
Author(s):  
L. JIN ◽  
S. XU ◽  
P. A. C. MAPLE ◽  
W. XU ◽  
K. E. BROWN
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Varicella Zoster Virus ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Chain Reactions ◽  
Varicella Zoster ◽  
Polymerase Chain Reactions ◽  
Set Up ◽  
The Uk

SummaryVaricella–zoster virus (VZV) infection (chickenpox) results in latency and subsequent reactivation manifests as shingles. Effective attenuated vaccines (vOka) are available for prevention of both illnesses. In this study, an amplicon-based sequencing method capable of differentiating between VZV wild-type (wt) strains and vOka vaccine is described. A total of 44 vesicular fluid specimens collected from 43 patients (16 from China and 27 from the UK) with either chickenpox or shingles were investigated, of which 10 had received previous vaccination. Four sets of polymerase chain reactions were set up simultaneously with primers amplifying regions encompassing four single nucleotide polymorphisms (SNPs), ‘69349-106262-107252-108111’. Nucleotide sequences were generated by Sanger sequencing. All samples except one had a wt SNP profile of ‘A-T-T-T’. The sample collected from a patient who received vaccine 7–10 days ago, along with VZV vaccine preparations, Zostavax and Baike-varicella gave a SNP profile ‘G-C-C-C’. The results show that this method can distinguish vaccine-derived virus from wt viruses from main four clades, (clades 1–4) and should be of utility worldwide.

scholarly journals Polymorphism of MUC1 gene in Vietnamese gastric cancer patients: a case-control study

2019 ◽  
Author(s):  
Lan Thi Ngoc Nguyen ◽  
Dzung Thi Ngoc Dang ◽  
Van Thanh Ta ◽  
Huy Quang Dang ◽  
Chuc Van Tran ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Family History ◽  
Single Nucleotide Polymorphisms ◽  
Cancer Patients ◽  
Nucleotide Polymorphisms ◽  
Mucin 1 ◽  
Single Nucleotide ◽  
History Of ◽  
Gastric Cancer Patients ◽  
Multifactor Regression

Abstract Background Gastric cancer is a malignant type of cancer associated with many factors such as environment, behavior, infection, and genetics, which include Single Nucleotide Polymorphism. A few studies revealed polymorphisms of the Mucin 1 gene have a role and significance as a susceptible factor contributing to gastric cancer. The aim of this research is to evaluate the association between Single Nucleotide Polymorphisms of the Mucin 1 gene and Vietnamese gastric cancer patients.Methods 302 gastric cancer patients and 304 controls were interviewed for social-economic characteristics, smoking and drinking status, personal and family history of gastric diseases. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism analysis. The association of Single Nucleotide Polymorphisms with gastric cancer was evaluated using multifactor regression models.Results AA genotype for rs4072037 was found to be highly associated with gastric cancer (OR: 2.07 (95% CI: 1.46-2.90). GG genotype for rs2070803 increased the risk of gastric cancer (OR:1.96 (95% CI: 1.37-2.78). These genotypes in combination with other factors such as old age, male gender, alcoholism and personal history of gastric disease also showed an increased risk of having gastric cancer.Conclusions rs4072037 and rs2070803 of Mucin 1 genes are two genotypic risk factors of gastric cancer. Those in combination with other factors such as gender, family history, smoking and drinking habits significantly increase the risk of gastric cancer.

scholarly journals Γενετικοί πολυμορφισμοί προφλεγμονωδών και αντιφλεγμονωδών κυτταροκινών και ευπάθεια των νεογνών και βρεφών στην οξεία μέση ωτίτιδα

2014 ◽  
Author(s):  
Σταυρούλα Ηλία
Keyword(s):  
Family History ◽  
Single Nucleotide Polymorphisms ◽  
Otitis Media ◽  
Inflammatory Cytokine ◽  
Early Infancy ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
History Of ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine

Background: Acute otitis media (AOM) is the most common childhood infection, and despite the lower prevalence in neonates and early infancy, serious complications can occur. Pathogenesis is multi-factorial and little is known on the immature host responses to pathogens during otitis media. Extensive studies on the complex cytokine network and its genetically determined regulation have highlighted the significance as determinants of susceptibility and outcome of AOM.Objective: In the current study we investigated the genetic predisposition of the immune host’s response as related to susceptibility, severity and outcome of AOM in early infancy. For this purpose we have chosen 8 single nucleotide polymorphisms (SNPs) of pro-inflammatory and anti-inflammatory cytokines: IL6 (-174 G→C), IL10 (-1082 G→A, -819 C→T, -592 C→A), TNFα (-308 G→A), INFγ (+874 A→T), TGFβ1 (codon 10 C→T, codon 25 G→C).Methods: Neonates and infants with AOM hospitalized in pediatric units of University Hospital and Venizeleion General Hospital, both in Heraklion, Crete, during 2005-2006 were included and followed-up for three consecutive years. Demographics, history, clinical manifestations, and relapses were recorded. Cytokine single nucleotide polymorphisms were determined by the polymerase chain reaction method. We studied predisposing clinical factors affecting severity and chronicity of the disease, as well as cytokine genotypes as related to susceptibility, clinical course and outcome of AOM. Gender, patient’s atopy, exposure to smoke, siblings, breast feeding, and family history of AOM or atopy were considered as potential covariates in the epidemiological analysis. Results: 96 infants were analyzed, 58 (60.4%) were boys, mean age at enrolment was 2.4 months (range 0.6-7.92), and 52 (54%) were younger than 3 months. At the end of follow-up period, 81 (84.4%) infants presented with recurrent AOM episodes. Gastro-esophageal regurgitation, patient’s atopy and positive family history of AOM were related to increased recurrence rates (p=0.01, p=0.01, and p=0.02 respectively). IL10 (-1082) A and TGFβ1 (codon 10) T minor alleles were related to older age of AOM onset than the wild-type genotypes (p=0.007 and p=0.0039 respectively). As compared to wild genotypes, IL10 (-592 C→A, -819 C→T, -1082 G→A) θαη TGFβ1 (codon 10 C→T) genotypes carrying the alternative gene were related to more AOM episodes (p<0.0001, p<0.0001, p<0.0001, and p=0.002, respectively) and need for tympanostomy tubes (p=0.021, p=0.021, p=0.036, and p=0.049, respectively). The associations remained significant for AOM onset and recurrence after adjusting for confounding factors (multiple regression analysis).Conclusions: Our findings suggest that anti-inflammatory cytokine IL10 and TGFβ1 genotypes influence AOM onset, number of recurrent episodes and tympanostomy tube placement. This evidence expands our understanding toward pathogenesis and outlines the anti-inflammatory cytokine implication in the middle ear inflammation. Immunomodulation of host gene expression and modification of certain polymorphisms could possibly play a significant role in susceptibility and outcome of AOM. Identification of genetically susceptible infants will allow for individualized treatment and prevention strategies.

scholarly journals Real-Time Polymerase Chain Reaction as a Method of Express Genetic Typing of Patients with Uterine Leiomyoma: An Example of Three Genetic Polymorphisms

Doctor Ru ◽  
2021 ◽  
Vol 20 (8) ◽  
pp. 7-11
Author(s):  
M.V. Kuznetsova ◽  
◽  
K.A. Svirepova ◽  
N.S. Sogoyan ◽  
A.I. Nikiforova ◽  
...  
Keyword(s):  
Family History ◽  
Single Nucleotide Polymorphisms ◽  
Real Time ◽  
Real Time Pcr ◽  
Uterine Leiomyoma ◽  
Direct Sequencing ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
History Of ◽  
Large Groups

Study Objective: To assess the efficacy of methods for DNA gene typing (direct sequencing and two variants of real-time PCR) for routine analysis of large groups; to compare the prevalence of genotypes of three single nucleotide polymorphisms in groups of women with uterine leiomyoma (with a separate analysis of a group with a family history of the disease) and in controls. Study Design: comparative study. Materials and Methods. Subjects were divided into groups using the case-control principle. DNA gene typing results for two groups of patients were analysed. Also, we analysed prevalence of genotypes in study group (patients with uterine leiomyoma) and in controls (patients without a history of uterine leiomyoma and a family history of the disease). The primary method used for genotyping was direct sequencing with genotype imaging. On the second stage, we tested two different PCR-based genotyping methods. Study Results. Patients with uterine leiomyoma were subject to genotyping using three single nucleotide polymorphisms (rs3020434, rs124577644, rs12637801) in ESR1, FBN2, and KCWMB2 introns. We have identified significant differences in prevalence of genotypes between the study group and controls. Polymorphism prevalence is statistically different between patients with leiomyomas, controls and women with a family history of the disease. It is demonstrated that the use of the two variants of real-time PCR testing instead of direct sequencing speeds up results; these methods are a less expensive and less labour-intensive tool for genotyping of single nucleotide polymorphisms in large groups. Conclusion. Real-time PCR testing can be used for express and efficient analysis of single nucleotide polymorphisms associated with uterine leiomyoma. Both methods (PCR genotyping with the use of oligonucleotide probes and analysis of high-resolution melting profiles) tested in this paper make it possible to get unambiguous results in 97–99% of samples. Keywords: uterine leiomyoma, single nucleotide polymorphisms, family proneness.

scholarly journals Unraveling Ambiguous NAT2 Genotyping Data

2008 ◽  
Vol 54 (8) ◽  
pp. 1390-1394 ◽  
Author(s):  
José A G Agúndez ◽  
Klaus Golka ◽  
Carmen Martínez ◽  
Silvia Selinski ◽  
Meinolf Blaszkewicz ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Drug Effects ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Nat2 Genotype ◽  
Drug Metabolizing Enzyme ◽  
New Variant ◽  
Nat2 Gene ◽  
Haplotype Mapping ◽  
Prediction Techniques

Abstract Background: Arylamine N-acetyltransferase 2 (CoASAc; NAT2, EC 2.3.1.5) is a drug-metabolizing enzyme that displays common polymorphisms leading to impaired drug metabolism and adverse drug effects. Determination of the N-acetyltransferase 2 (arylamine N-acetyltransferase) (NAT2) genotype in clinical practice is hampered by the occurrence of ambiguous haplotype combinations that may lead to patient misclassification. We determined the frequencies for ambiguous NAT2 haplotypes and diplotypes in a white population and investigated the use of PHASE v2.1.1, a statistical program for haplotype reconstruction, to clarify this ambiguity and classify individuals according to their acetylation status. Methods: By means of allele-specific haplotype mapping and sequencing, we determined the haplotypes for 7 common single-nucleotide polymorphisms in the NAT2 gene (n = 2624 haplotypes). To test the performance of PHASE, actual genotypes were deconstructed and then reconstructed by haplotype prediction. Results: We identified 21 NAT2 allelic variants, including a new variant allele that combines the single-nucleotide polymorphisms rs1801279, rs1799929, and rs1208. In contrast, the previously described variant alleles *5G, *5J, *6E, *7A, *11A, *11B, and *14B were not identified in the study population. Ambiguous haplotypes were observed in 98 alleles (3.7%), and ambiguous diplotypes were observed in 64 individuals (4.9%). Eleven individuals (0.8%) were misclassified by the use of haplotype prediction. Conclusions: Ambiguous NAT2 genotyping data are common. Actual NAT2 genotypes cannot be fully determined by haplotype prediction techniques. This study provides real haplotype data that can be used as a guide to convert NAT2 haplotypes and diplotypes into actual genotypes in white individuals.

scholarly journals Association of Single Nucleotide Polymorphisms with Dyslipidemia in Antiretroviral Exposed HIV Patients in a Ghanaian population

2019 ◽  
Author(s):  
Christian Obirikorang ◽  
Emmanuel Acheampong ◽  
Lawrence Quaye ◽  
Joseph Yorke ◽  
Ernestine Kubi Amos-Abanyie ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Hiv Patients ◽  
Single Nucleotide ◽  
Significant Difference ◽  
Baseline Information ◽  
Healthy Control ◽  
History Of ◽  
Study Participants ◽  
Rare Homozygote

AbstractDyslipidemia is a potential complication of long-term usage of antiretroviral therapy (ART) and also known to be associated with genetic factors. The host genetic variants associated with dyslipidemia in HIV patients on ART in Ghana have not been fully explored. The study constituted a total of 289 HIV-infected patients on stable ART for at least a year and 85 aged matched apparently healthy control subjects with no history of HIV and dyslipidemia. Fasting blood was collected into EDTA tube for lipids measurements. Lipid profiles were determined as a measure of dyslipidemia. HIV-infected patients were categorized into two groups; those with dyslipidemia(HIV-Dys+) (n=90; 31.1%) and without dyslipidemia (n=199; 68.9%) based on the NCEP-ATP III criteria. Four candidate single nucleotide polymorphisms (SNPs) genes (ABCA1-rs2066714, LDLR-rs6511720, APOA5-rs662799 and DSCAML1-rs10892151) were determined. Genotyping was performed on isolated genomic DNA of study participants using PCR followed by a multiplex Ligation Detection Reaction (LDR). The percentage of the population who had the rare homozygote alleles for rs6511720 (T/T), rs2066714 (G/G), and rs10892151 (T/T) and rs662799 (G/G) among HIV+Dys+ subjects were 5.5%, 14.4%, 6.6% and 10.0%; 2.0% 9.1%, 6.5% and 4.0% among HIV+Dys- subjects while 3.5%, 4.7%, 4.7% and 2.4% were observed in HIV-Dys- subjects. Statistically significant difference in genotypic prevalence of APOA5 polymorphisms was observed among different groups (p=0.0196). Compared to the AA genotype of the APOA5 polymorphisms, individuals with the rare homozygote genotype [aOR =4.01, 95%CI(1.57-22.39), p=0.004] were significantly more likely to develop dyslipidemia after controlling for age, gender, treatment duration and CD4 counts among the HIV+Dys+ subjects. There was also a significant associated between GG genotype of ABCA1 and dyslipidemia [aOR =3.29, 95% (1.08 −12.43); p=0.042]. Individuals with the rare homozygote variant (GG) of APOA5 (rs662799) were significantly associated with increased likelihood of developing dyslipidemia [OR =2.24, 95% CI (1.20 −6.83); p=0.0370] holding other variables constant in the HIV+Dys- subjects. Our data accentuate the presence of SNPs in four candidate genes and its association with dyslipidemia among HIV patients exposed to ART in the Ghanaian population especially variants in APOA5-rs662799 ABCA1-rs2066714 respectively. These findings provide baseline information that necessitates a pre-symptomatic strategy for monitoring dyslipidemia in ART-treated HIV patients. There is a need for longitudinal studies to validate a comprehensive number of SNPs and its association with dyslipidemia.

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