scholarly journals Real-Time PCR for Dihydrofolate Reductase Gene Single-Nucleotide Polymorphisms in Plasmodium vivax Isolates

2004 ◽  
Vol 48 (7) ◽  
pp. 2581-2587 ◽  
Author(s):  
Sara Brega ◽  
Frédérique de Monbrison ◽  
Carlo Severini ◽  
Rachanee Udomsangpetch ◽  
Inge Sutanto ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
World Health ◽  
Nucleotide Polymorphisms ◽  
Hybridization Probe ◽  
Mutant Type ◽  
Single Nucleotide ◽  
Infected Blood ◽  
Reductase Gene ◽  
Health Organization ◽  
National Programs

ABSTRACT Mutations in the dhfr gene of Plasmodium vivax (pvdhfr) are associated with resistance to the antifolate antimalarial drugs. Polymorphisms in the pvdhfr gene were assessed by hybridization probe technology on the LightCycler instrument with 134 P. vivax-infected blood samples from Turkey (n = 24), Azerbaijan (n = 39), Thailand (n = 16), Indonesia (n = 53), and travelers (n = 19). Double mutations (S58R and S117N) or quadruple mutations (F57L/I, S58R, T61M, and S117N) in the pvdhfr genes were found in all Thai samples (100%). pvdhfr mutant-type alleles were significantly more common in samples from travelers (42%) than in those from patients from Indonesia (5%). Surprisingly, the pvdhfr single-mutation allele (S117N) was identified at a high frequency in parasites from Turkey and Azerbaijan (71 and 36%, respectively), where sulfadoxine-pyrimethamine is not recommended for the treatment of P. vivax malaria by the World Health Organization and the Malaria National Programs.

scholarly journals Avaliação das Variantes Genéticas dos Genes AMELX e ENAM na Cárie Dentária em Adolescentes

2021 ◽  
Vol 24 (5-esp.) ◽  
pp. 650-654
Author(s):  
Gabriela Paschoalini Romagni ◽  
Paula Marino Costa ◽  
Sandra Mara Maciel ◽  
Maria Paula Jacobucci ◽  
Regina Célia Poli-Frederico
Keyword(s):  
Genetic Component ◽  
World Health ◽  
Caries Experience ◽  
Nucleotide Polymorphisms ◽  
Chi Square ◽  
Single Nucleotide ◽  
Significance Level ◽  
Exact Test ◽  
Polymerase Chain ◽  
Health Organization

A doença cárie é considerada, atualmente, como biofilme sacarose dependente, entretanto, estudos recentes apontam que fatores genéticos também podem influenciar seu desenvolvimento. Variantes nos gene amelogenina (AMELX) e enamelina (ENAM), responsáveis pela formação do esmalte, têm sido propostas como potencialmente envolvidos na doença. O objetivo deste estudo foi avaliar se a ocorrência de cárie dentária em adolescentes está relacionado às variantes nos genes AMELX e ENAM. Para a avaliação da prevalência de cárie foi utilizado o índice de dentes cariados, perdidos e obturados (CPO-D), segundo critérios da Organização Mundial de Saúde. As amostras de DNA foram extraídas das células da mucosa oral. Para a análise dos polimorfismos de nucleotídeo único (SNPs) dos genes AMELX (rs17878486) e ENAM (rs7671281) foi utilizada  a técnica de amplificação de fragmentos de DNA pela reação em cadeia da polimerase foi realizada (PCR) em tempo real pelo sistema TaqMan (Applied Biosystems, Foster City, EUA). Para a análise estatística, foi utilizado o teste exato de Fisher e qui-quadrado com nível de significância de 5%. Apenas os fatores socioeconômicos influenciaram a experiência de cárie. Concluiu-se que o componente genético, na população deste estudo, não influenciou o desenvolvimento da cárie.   Palavras-chave: Polimorfismo genético. Adolescentes. Esmalte.   Abstract Caries disease is currently considered a sucrose-dependent biofilm, however recent studies indicate that a genetic component can also influence its development. Variants in the amelogenin (AMELX) and enamelin (ENAM) genes, responsible for the enamel formation, have been proposed as potentially involved in the disease. The purpose of this study was to evaluate whether the occurrence of dental caries in adolescents is related to variants in the AMELX and ENAM genes. To assess the caries prevalence, the index of decayed, missing and filled teeth (DMFT) were used, according to World Health Organization criteria. DNA samples were extracted from oral mucosa cells. For the analysis of single nucleotide polymorphisms (SNPs) of the AMELX (rs17878486) and ENAM (rs7671281) genes, the amplifying DNA fragments technique  by the polymerase chain reaction was performed (PCR) in real time by the TaqMan system (Applied Biosystems, Foster City, USA). For the statistical analysis, Fisher's exact test and chi-square were used with a 5% significance level. Only socioeconomic factors influenced the caries experience. It was concluded that the genetic component in the population of this study, did not influence the development of caries.   Keywords: Genetic polymorphism. Adolescents. Enamel.

scholarly journals MC4R Single Nucleotide Polymorphisms Were Associated with Metabolically Healthy and Unhealthy Obesity in Chinese Northern Han Populations

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Luying Gao ◽  
Linjie Wang ◽  
Hongbo Yang ◽  
Hui Pan ◽  
Fengying Gong ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Cardiovascular Complications ◽  
Normal Weight ◽  
World Health ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Flight Mass Spectrometry ◽  
Metabolically Healthy Obese ◽  
Metabolically Healthy ◽  
Health Organization

Melanocortin-4 receptor (MC4R) has been reported to be associated with the risk of obesity, and metabolically unhealthy obese (MUHO) patients tend to have a greater risk of cardiovascular complications than metabolically healthy obese (MHO) patients. Therefore, we aimed to study single nucleotide polymorphisms (SNPs) in the MC4R gene associated with metabolically healthy and unhealthy obesity in Chinese Northern Han populations. A total of 1100 Chinese Northern Han subjects were recruited and divided into four groups according to the criteria of the Adult Treatment Panel-III (ATP-III) and World Health Organization (WHO): MUHO (n = 300), MHO (n = 196), metabolic unhealthy normal weight (MUH-NW) (n = 303), and metabolic healthy normal weight (MH-NW) (n = 301). DNA samples were extracted, and six SNPs of the MC4R gene, including rs2331841, rs656710, rs17782313, rs571312, rs12970134, and rs11872992, were genotyped with the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) method. Among the six SNPs of the MC4R gene, rs2331841 (A/G) was the most significant and could account for 0.9% of obesity etiology. Compared with the normal weight group, rs2331841 of the MC4R gene was associated with obesity (P=0.032). The obesity risk of subjects with the AG genotype in the rs2331841 site was 82% higher than the risk of those with the GG genotype (β = 0.60, OR = 1.82, P=0.030). After adjusting for sex and age, the frequency of the A allele in the rs2331841 site was higher in the MUHO group than in the MH-NW group (27.9% vs. 21.1%, respectively, OR = 1.49, 95% CI 1.14–1.96, P=0.005) and in the MUHO group than in the MHO group (27.9% vs. 22.3%, respectively, OR = 1.39, 95% CI 1.02–1.92, P=0.039). Among the three genotypes of rs2331841, the subjects with the AA/AG genotype had higher diastolic blood pressure (DBP) than those with the GG genotype. Our data first suggest that SNPs in the rs2331841 site of the MC4R gene are closely related to obesity and its related metabolic disorders in Chinese Northern Han populations. The participants with an A allele of rs2331841 had a higher risk of obesity and MUHO than other participants.

IL-10-592 A/C Gene Polymorphism and Cytokine Levels are Associated with Susceptibility to Drug Resistance in Tuberculosis

2020 ◽  
Vol 8 (3) ◽  
pp. 103-112
Author(s):  
Atefeh SADEGHI SHERMEH ◽  
Majid KHOSHMIRSAFA ◽  
Ali-Akbar DELBANDI ◽  
Payam TABARSI ◽  
Esmaeil MORTAZ ◽  
...  
Keyword(s):  
Serum Levels ◽  
World Health ◽  
Control Group ◽  
Drug Resistant ◽  
Nucleotide Polymorphisms ◽  
Genotype Frequencies ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
Health Organization ◽  
And Function

Introduction: Tuberculosis (TB) and especially resistant forms of it have a substantial economic burden on the community health system for diagnosis and treatment each year. Thus, investigation of this field is a priority for the world health organization (WHO). Cytokines play important roles in the relationship between the immune system and tuberculosis. Genetic variations especially single nucleotide polymorphisms (SNPs) impact cytokine levels and function against TB. Material and Methods: In this research SNPs in IFN-γ (+874 T/A) and IL-10 (-592 A/C) genes, and the effects of these SNPs on cytokine levels in a total of 87 tuberculosis patients and 100 healthy controls (HCs) were studied. TB patients divided into two groups: 1) 67 drug-sensitive (DS-TB) and 2) 20 drug-resistant (DR-TB) according to drug sensitivity test using polymerase chain reaction (PCR). For the genotyping of two SNPs, the PCR-based method was used and IFN-γ and IL-10 levels were measured by ELISA in pulmonary tuberculosis (PTB) and control group. Results: In -592A/C SNP, only two genotypes (AA, AC) were observed and both genotypes showed statistically significant differences between DR-TB and HCs (p=0.011). IL-10 serum levels in PTB patients were higher than HCs (p=0.02). The serum levels of IFN-γ were significantly higher in DS-TB patients than that of the other two groups (p<0.001); however, no significant differences were observed for allele and genotype frequencies in IFN-γ +874. Conclusions: Our results suggest that the SNP at -592 position of IL-10 gene may be associated with the susceptibility to DR-TB. However, further investigation is necessary. Keywords: Polymorphism, IFN-γ, IL-10, tuberculosis, drug-resistant tuberculosis

scholarly journals Spatiotemporal Changes in Plasmodium vivax msp142 Haplotypes in Southern Mexico: From the Control to the Pre-Elimination Phase

2022 ◽  
Vol 10 (1) ◽  
pp. 186
Author(s):  
Alejandro Flores-Alanis ◽  
Lilia González-Cerón ◽  
Frida Santillán-Valenzuela ◽  
Cecilia Ximenez ◽  
Marco A. Sandoval-Bautista ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Haplotype Diversity ◽  
Haplotype Network ◽  
Southern Mexico ◽  
Single Nucleotide ◽  
Genetic Studies ◽  
Elimination Phase ◽  
Infected Blood ◽  
Malaria Species ◽  
Over Time

For 20 years, Plasmodium vivax has been the only prevalent malaria species in Mexico, and cases have declined significantly and continuously. Spatiotemporal genetic studies can be helpful for understanding parasite dynamics and developing strategies to weaken malaria transmission, thus facilitating the elimination of the parasite. The aim of the current contribution was to analyze P. vivax-infected blood samples from patients in southern Mexico during the control (1993–2007) and pre-elimination phases (2008–2011). Nucleotide and haplotype changes in the pvmsp142 fragment were evaluated over time. The majority of multiple genotype infections occurred in the 1990s, when the 198 single nucleotide sequences exhibited 57 segregating sites, 64 mutations, and 17 haplotypes. Nucleotide and genetic diversity parameters showed subtle fluctuations from across time, in contrast to the reduced haplotype diversity and the increase in the R2 index and Tajima’s D value from 2008 to 2011. The haplotype network consisted of four haplogroups, the geographical distribution of which varied slightly over time. Haplogroup-specific B-cell epitopes were predicted. Since only high-frequency and divergent haplotypes persisted, there was a contraction of the parasite population. Given that 84% of haplotypes were exclusive to Mesoamerica, P. vivax flow is likely circumscribed to this region, representing important information for parasite surveillance.

scholarly journals Using Mycobacterium tuberculosis Single-Nucleotide Polymorphisms To Predict Fluoroquinolone Treatment Response

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
Marva Seifert ◽  
Edmund Capparelli ◽  
Donald G. Catanzaro ◽  
Timothy C. Rodwell
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Single Nucleotide Polymorphisms ◽  
Specific Resistance ◽  
Therapeutic Targets ◽  
World Health ◽  
Population Pharmacokinetic ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Content Type ◽  
Level Increase

ABSTRACT Clinical phenotypic fluoroquinolone susceptibility testing of Mycobacterium tuberculosis is currently based on M. tuberculosis growth at a single critical concentration, which provides limited information for a nuanced clinical response. We propose using specific resistance-conferring M. tuberculosis mutations in gyrA together with population pharmacokinetic and pharmacodynamic modeling as a novel tool to better inform fluoroquinolone treatment decisions. We sequenced the gyrA resistance-determining region of 138 clinical M. tuberculosis isolates collected from India, Moldova, Philippines, and South Africa and then determined each strain’s MIC against ofloxacin, moxifloxacin, levofloxacin, and gatifloxacin. Strains with specific gyrA single-nucleotide polymorphisms (SNPs) were grouped into high or low drug-specific resistance categories based on their empirically measured MICs. Published population pharmacokinetic models were then used to explore the pharmacokinetics and pharmacodynamics of each fluoroquinolone relative to the empirical MIC distribution for each resistance category to make predictions about the likelihood of patients achieving defined therapeutic targets. In patients infected with M. tuberculosis isolates containing SNPs associated with a fluoroquinolone-specific low-level increase in MIC, models suggest increased fluoroquinolone dosing improved the probability of achieving therapeutic targets for gatifloxacin and moxifloxacin but not for levofloxacin and ofloxacin. In contrast, among patients with isolates harboring SNPs associated with a high-level increase in MIC, increased dosing of levofloxacin, moxifloxacin, gatifloxacin, or ofloxacin did not meaningfully improve the probability of therapeutic target attainment. We demonstrated that quantifiable fluoroquinolone drug resistance phenotypes could be predicted from rapidly detectable gyrA SNPs and used to support dosing decisions based on the likelihood of patients reaching therapeutic targets. Our findings provide further supporting evidence for the moxifloxacin clinical breakpoint recently established by the World Health Organization.

scholarly journals Genetic Variation in Cytokine-Related Genes and Migraine Susceptibility

2013 ◽  
Vol 16 (6) ◽  
pp. 1079-1086 ◽  
Author(s):  
Shani Stuart ◽  
Bridget H. Maher ◽  
Heidi Sutherland ◽  
Miles Benton ◽  
Astrid Rodriguez ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Disease Risk ◽  
Sterile Inflammation ◽  
World Health ◽  
Risk Haplotype ◽  
Nucleotide Polymorphisms ◽  
And Gender ◽  
Health Organization ◽  
Tnf Gene ◽  
Lymphotoxin Α

Migraine is classified by the World Health Organization (WHO) as being one of the top 20 most debilitating diseases. According to the neurovascular hypothesis, neuroinflammation may promote the activation and sensitisation of meningeal nociceptors, inducing the persistent throbbing headache characterized in migraine. The tumor necrosis factor (TNF) gene cluster, made up of TNFα, lymphotoxin α (LTA), and lymphotoxin β (LTB), has been implicated to influence the intensity and duration of local inflammation. It is thought that sterile inflammation mediated by LTA, LTB, and TNFα contributes to threshold brain excitability, propagation of neuronal hyperexcitability and thus initiation and maintenance of a migraine attack. Previous studies have investigated variants within the TNF gene cluster region in relation to migraine susceptibility, with largely conflicting results. The aim of this study was to expand on previous research and utilize a large case-control cohort and range of variants within the TNF gene cluster to investigate the role of the TNF gene cluster in migraine. Nine single nucleotide polymorphisms (SNPs) were selected for investigation as follows: rs1800683, rs2229094, rs2009658, rs2071590, rs2239704, rs909253, rs1800630, rs1800629, and rs3093664. No significant association with migraine susceptibility was found for any of the SNPs tested, with further testing according to migraine subtype and gender also showing no association for disease risk. Haplotype analysis showed that none of the tested haplotypes were significantly associated with migraine.

DNA variants in the dihydrofolate reductase gene and outcome in childhood ALL

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3692-3700 ◽  
Author(s):  
Stéphanie Dulucq ◽  
Geneviève St-Onge ◽  
Vincent Gagné ◽  
Marc Ansari ◽  
Daniel Sinnett ◽  
...  
Keyword(s):  
Dihydrofolate Reductase ◽  
Lymphoblastic Leukemia ◽  
Luciferase Expression ◽  
Nucleotide Polymorphisms ◽  
Promoter Polymorphisms ◽  
Single Nucleotide ◽  
Childhood All ◽  
Reductase Gene ◽  
Haplotype 1 ◽  
Folate Cycle

Abstract Dihydrofolate reductase (DHFR) is the major target of methotrexate (MTX), a key component in childhood acute lymphoblastic leukemia (ALL) treatment. A total of 15 polymorphisms in DHFR promoter were analyzed, and 3 sites (C−1610G/T, C−680A, and A−317G) were identified as sufficient to define observed haplotypes (tag single nucleotide polymorphisms [tagSNPs]). These polymorphisms were investigated for association with treatment response in 277 children with ALL. Lower event-free survival (EFS) was associated with homozygosity for the allele A−317 and C−1610 (P = .03 and .02), and with the haplotype *1, defined by both C−1610 and A−317 alleles (P = .03). The haplotype *1 conferred higher transcriptional activity (P < .01 compared with haplotypes generating minimal luciferase expression). Quantitative mRNA analysis showed higher DHFR levels for particular haplotype *1 carriers (P < .01). The analysis combining haplotype *1 with thymidylate synthase (TS) and cyclin D1 (CCND1) genotypes previously shown to affect ALL outcome showed that the number of event-predisposing genotypes was associated with increasingly lower EFS (P < .001). In conclusion, DHFR promoter polymorphisms are associated with worse ALL outcome, likely due to a higher DHFR expression. Combined effects among genes of the folate cycle can further accentuate differences in the response to the treatment.

scholarly journals A novel point mutation in the N gene of SARS-CoV-2 may affect the detection of the virus by RT-qPCR

2021 ◽  
Author(s):  
Mohammad Rubayet Hasan ◽  
Sathyavathi Sundararaju ◽  
Chidambaram Manickam ◽  
Faheem Mirza ◽  
Hamad Al-Hail ◽  
...  
Keyword(s):  
Viral Genome ◽  
Large Scale ◽  
Target Genes ◽  
Cytidine Deaminase ◽  
World Health ◽  
N Gene ◽  
Single Nucleotide ◽  
E Gene ◽  
Reverse Transcription Pcr ◽  
Health Organization

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, laboratory testing to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time reverse transcription PCR (RT-qPCR) has played a central role in mitigating the spread of the virus (1). Soon after the viral genome sequences were available, several RT-qPCR assays were developed and made available by World Health Organization (WHO) for public use (https://www.who.int/docs/default-source/coronaviruse/whoinhouseassays.pdf). The primer and probe sequences for these assays were chosen from multiple target genes within the viral genome such as the E gene, RdRp gene, ORF1ab and N gene. Many commercial and laboratory-developed assays were developed for SARS-CoV-2 detection based on these primer and probe sequences. The large-scale sustained person-to-person transmission of SARS-CoV-2 has led to many mutational events, some of which may affect the sensitivity and specificity of available PCR assays (2). Recently, mutations in the E gene (C26340T) and N gene (C29200T) were reported affecting the detection of target genes by two commercial assays in 8 and 1 patients, respectively. Interestingly, both mutations are of C>T type, a common single nucleotide polymorphism (SNP) that may be associated with strong host cell mRNA editing mechanisms known as APOBEC cytidine deaminase (3, 4). Another study found a G to U substitution in position 29140 that affected the sensitivity of detection of N gene-based assays (5). Here we report a novel N gene mutation (C29200A) seen in 3 patients, which affected the detection of SARS-CoV-2 N gene by a commercial assay.

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