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Transactions of the Royal Society of... Aug 2021Multidrug-resistant TB (MDR-TB) outbreaks have occurred in the Thamaka district, Kanchanaburi province in Thailand.
BACKGROUND
Multidrug-resistant TB (MDR-TB) outbreaks have occurred in the Thamaka district, Kanchanaburi province in Thailand.
METHODS
Seventy-two isolates, which included 7% mono-, 30.6% MDR and extensively drug-resistant TB (XDR-TB), were genotyped by spoligotyping, mycobacterial interspersed repetitive unit-variable-number tandem repeat (MIRU-VNTR) and single nucleotide polymorphism genotyping, and their drug resistance was analysed.
RESULTS
The spoligotyping results showed that Beijing spoligo-international type (SIT)1 was predominant (n=38; 52.8%) while the remaining were non-Beijing sublineages (n=34). The MIRU-VNTR analysis showed that Beijing isolates, most of which belonged to the modern type (n=37), formed 5 clusters and 13 individual patterns. In katG, only mutation Ser315Thr was identified. In rpoB, Ser531Leu was predominant, except for His526Arg and Leu533Pro, which were found in two isolates. A cluster of 14 Beijing strains contained these common mutations and shared the MIRU-VNTR genotype with isolates in the Thamaka district that had spread previously. Two U SIT523 isolates contained the mutations A1400G in rrs and Asp94Gly in gyrA genes, indicating a spread of XDR-TB.
CONCLUSIONS
Most mutations were associated with drug resistance and the specific MDR Beijing and XDR-TB in U SIT523 isolates remain. This genotyping is a key tool for tracking TB transmission in the Thamaka district of Thailand.
Topics: Antitubercular Agents; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Genotype; Humans; Minisatellite Repeats; Mycobacterium tuberculosis; Thailand; Tuberculosis, Multidrug-Resistant
PubMed: 33320938
DOI: 10.1093/trstmh/traa148 -
Journal of Neural Transmission (Vienna,... Nov 2021Epigenome-wide studies report higher methylation among women than men with decreasing levels with age. Little is known about associations of sex and age with methylation...
Epigenome-wide studies report higher methylation among women than men with decreasing levels with age. Little is known about associations of sex and age with methylation of monoamine oxidase A (MAOA). Methylation of the first exonic and partial first intronic region of MAOA has been shown to strengthen associations of interactions of MAOA-uVNTR genotypes and adversity with aggression and substance misuse. Our study examined associations of sex and age with MAOA first exon and intron methylation levels in 252 women and 157 men aged 14-73 years. Participants included adolescents recruited at a substance misuse clinic, their siblings and parents, and healthy women. Women showed ~ 50% higher levels of exonic, and ~ 15% higher intronic, methylation than men. Methylation levels were similar between younger (M = 22.7 years) and older (M = 46.1 years) participants, and stable across age. Age modified few associations of methylation levels with sex. MAOA genotypes modified few associations of methylation with sex and age. Higher methylation levels among women were not explained by genotype, nor interaction of genotype and sexual abuse. Findings were similar after adjusting for lifetime diagnoses of substance dependence (women = 24.3%; men = 34.2%). Methylation levels were higher among women who experienced sexual abuse than women who did not. Results extend on prior studies by showing that women display higher levels of methylation than men within first intronic/exonic regions of MAOA, which did not decrease with age in either sex. Findings were not conditioned by genotype nor interactions of genotype and trauma, and indicate X-chromosome inactivation.
Topics: Adolescent; Adult; Aged; Aggression; Female; Genotype; Humans; Male; Methylation; Middle Aged; Minisatellite Repeats; Monoamine Oxidase; Sex Offenses; Young Adult
PubMed: 34424394
DOI: 10.1007/s00702-021-02403-2 -
The American Journal on Addictions Jul 2019Disulfiram has been beneficial in treating cocaine addiction in several studies. Patients with two SLC6A3 (DAT1) rs28363170 10-repeat alleles who have with genetically... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
Disulfiram has been beneficial in treating cocaine addiction in several studies. Patients with two SLC6A3 (DAT1) rs28363170 10-repeat alleles who have with genetically high dopamine transporter (DAT) levels may benefit from increased dopamine levels resulting from disulfiram treatment.
METHODS
After stabilization for 2 weeks on methadone, 70 cocaine and opioid codependent patients were randomized into disulfiram and placebo groups for 12 weeks of treatment. We genotyped the SLC6A3 (DAT1) 40 bp 3'-untranslated region variable number tandem repeat variant and evaluated its role in moderating disulfiram efficacy for cocaine dependence.
RESULTS
Among the 10,10-repeat genotype group, cocaine-positive urines dropped from 78% to 48% and from 80% to 75% among the 9-repeat carrier group in the disulfiram group (P = 0.0001, with an effect size of 0.09). No difference was observed in cocaine-positive urines in the placebo group between the 10,10-repeat genotype and the 9-allele carrier patients.
CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE
We found that patients with genetically higher DAT levels had better treatment outcomes with disulfiram pharmacotherapy of cocaine dependence than those with lower DAT levels. (Am J Addict 2019;28:311-317).
Topics: Acetaldehyde Dehydrogenase Inhibitors; Adult; Alleles; Biomarkers; Cocaine-Related Disorders; Disulfiram; Dopamine Plasma Membrane Transport Proteins; Female; Genetic Markers; Genotype; Humans; Male; Minisatellite Repeats; Pharmacogenetics; Polymorphism, Genetic; Treatment Outcome
PubMed: 31087723
DOI: 10.1111/ajad.12891 -
Journal of Applied Biomedicine Dec 2021Nephrotic syndrome (NS) might be caused by a kidney disorder or it can be a secondary disease. Untreated or resistant to treatment, NS stimulates glomerular damage that...
INTRODUCTION
Nephrotic syndrome (NS) might be caused by a kidney disorder or it can be a secondary disease. Untreated or resistant to treatment, NS stimulates glomerular damage that reduces the kidney function. This reduction leads to the end stage of renal failure. Therefore, it is very important to diagnose NS early, with the aim of inhibiting or lessening its associated morbidity and mortality.
METHODS
Gene polymorphism analysis for the three genes eNOS 27 bp VNTR, GSTP1 and IL-10(1082 G/A) were checked in 98 children with NS and 101 control subjects.
RESULTS
eNOS 27 bp VNTR genotypes and alleles are significantly different in the group of 98 children with NS compared to the 101 control subjects. The frequencies of ab and bb genotypes are significantly lower in patients than in the control group (ab: 17.2% vs. 22.8%; OR: 0.19; 95% CI: 0.06-0.58; p = 0.0026 & bb: 54.7% vs. 70.3%; OR: 0.19; 95% CI: 0.07-0.5; p = 0.0004). However, neither GSTP1 nor IL-10(1082 G/A) genotypes showed any significant difference in both groups.
CONCLUSIONS
eNOS 27 bp VNTR gene might be considered as an independent risk factor in the early prediction of nephrotic syndrome incidence, which may help prevent/reduce the occurrence of other complications associated with the late diagnosis and treatment of the disease.
Topics: Alleles; Child; Egypt; Female; Genotype; Glutathione S-Transferase pi; Humans; Interleukin-10; Male; Minisatellite Repeats; Nephrotic Syndrome; Nitric Oxide Synthase Type III
PubMed: 34907742
DOI: 10.32725/jab.2021.022 -
International Journal of Molecular... Dec 2020Epilepsy is a neurological disease with different clinical forms and inter-individuals heterogeneity, which may be associated with genetic and/or epigenetic...
Epilepsy is a neurological disease with different clinical forms and inter-individuals heterogeneity, which may be associated with genetic and/or epigenetic polymorphisms of tandem-repeated noncoding DNA. These polymorphisms may serve as predictive biomarkers of various forms of epilepsy. ACAP3 is the protein regulating morphogenesis of neurons and neuronal migration and is an integral component of important signaling pathways. This study aimed to carry out an association analysis of the length polymorphism and DNA methylation of the UPS29 minisatellite of the gene in patients with epilepsy. We revealed an association of short UPS29 alleles with increased risk of development of symptomatic and cryptogenic epilepsy in women, and also with cerebrovascular pathologies, structural changes in the brain, neurological status, and the clinical pattern of seizures in both women and men. The increase of frequency of hypomethylated UPS29 alleles in men with symptomatic epilepsy, and in women with both symptomatic and cryptogenic epilepsy was observed. For patients with hypomethylated UPS29 alleles, we also observed structural changes in the brain, neurological status, and the clinical pattern of seizures. These associations had sex-specific nature similar to a genetic association. In contrast with length polymorphism epigenetic changes affected predominantly the long UPS29 allele. We suppose that genetic and epigenetic alterations UPS29 can modify expression and thereby affect the development and clinical course of epilepsy.
Topics: Alleles; Biomarkers; DNA Methylation; Epilepsy; Female; GTPase-Activating Proteins; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Male; Membrane Transport Proteins; Minisatellite Repeats; Mitochondrial Proteins; Phenotype; Polymorphism, Genetic; Sex Factors
PubMed: 33276684
DOI: 10.3390/ijms21239206 -
Frontiers in Cellular and Infection... 2023The epidemiological situation of tuberculosis (TB) in Poland urges for its continuous and scrupulous monitoring. The objective of this study was to explore the genetic...
INTRODUCTION
The epidemiological situation of tuberculosis (TB) in Poland urges for its continuous and scrupulous monitoring. The objective of this study was to explore the genetic diversity of multidrug-resistant (MDR) and drug-susceptible (DS) isolates from Poland with a combination of spoligotyping and high-resolution mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) analysis. The results were placed in the Northern and Eastern Europe context.
METHODS
The study included 89 (39 MDR and 50 DS) isolates collected from as many patients between 2018 and 2021 in Poland. The analysis was done using spoligotyping, and MIRU-VNTR typing at 24 standard loci. The data were compared to those available on Poland and neighbors and global datasets.
RESULTS
The main identified families were Beijing (28.1%) and Haarlem (16.8%) while 34.8% of isolates were in the heterogeneous L4-unclassified group. Although the Beijing family was the most prevalent (61.5%) among MDR-TB cases, it accounted for only 2% of DS isolates. Among foreign-born patients, a higher ratio of MDR isolates were observed when compared with those who Poland-born (64.3% vs. 40%). Furthermore, all patients from the Former Soviet Union (FSU) countries were infected with MDR-TB.
DISCUSSION
Whereas DS population in Poland is dominated by L4 isolates, MDR isolates are mostly of the Beijing genotype. The rise in the prevalence of the Beijing isolates in Poland, coupled with high proportion of the Beijing genotype among foreign-born TB patients may reflect an ongoing transmission of this family, imported to Poland mainly from FSU countries.
Topics: Humans; Mycobacterium tuberculosis; Phylogeny; Beijing; Poland; Tuberculosis; Tuberculosis, Multidrug-Resistant; Genotype; Minisatellite Repeats
PubMed: 37009494
DOI: 10.3389/fcimb.2023.1161905 -
Forensic Science International. Genetics Sep 2021Birds of prey have suffered persecution for centuries through trapping, shooting, poisoning and theft from the wild to meet the demand from egg collectors and falconers;...
Birds of prey have suffered persecution for centuries through trapping, shooting, poisoning and theft from the wild to meet the demand from egg collectors and falconers; they were also amongst the earliest beneficiaries of DNA testing in wildlife forensics. Here we report the identification and characterisation of 14 novel tetramer, pentamer and hexamer short tandem repeat (STR) markers which can be typed either by capillary electrophoresis or massively parallel sequencing (MPS) and apply them to historical casework samples involving 49 peregrine falcons, 30 of which were claimed to be the captively bred offspring of nine pairs. The birds were initially tested in 1994 with a multilocus DNA fingerprinting probe, a sex test and eight single-locus minisatellite probes (SLPs) demonstrating that 23 birds were unrelated to the claimed parents. The multilocus and SLP approaches were highly discriminating but extremely time consuming and required microgram quantities of high molecular weight DNA and the use of radioisotopes. The STR markers displayed between 2 and 21 alleles per locus (mean = 7.6), lengths between 140 and 360 bp, and heterozygosities from 0.4 to 0.93. They produced wholly concordant conclusions with similar discrimination power but in a fraction of the time using a hundred-fold less DNA and with standard forensic equipment. Furthermore, eleven of these STRs were amplified in a single reaction and typed using MPS on the Illumina MiSeq platform revealing eight additional alleles (three with variant repeat structures and five solely due to flanking SNPs) across four loci. This approach gave a random match probability of < 1E-9, and a parental pair false inclusion probability of < 1E-5, with a further ten-fold reduction in the amount of DNA required (~3 ng) and the potential to analyse mixed samples. These STRs will be of value in monitoring wild populations of these key indicator species as well as for testing captive breeding claims and establishing a database of captive raptors. They have the potential to resolve complex cases involving trace, mixed and degraded samples from raptor persecution casework representing a significant advance over the previously applied methods.
Topics: Animals; Animals, Wild; Crime; DNA; DNA Fingerprinting; Electrophoresis, Capillary; High-Throughput Nucleotide Sequencing; Microsatellite Repeats; Minisatellite Repeats; Polymorphism, Single Nucleotide; Sequence Analysis, DNA
PubMed: 34174583
DOI: 10.1016/j.fsigen.2021.102550 -
PloS One 2019Acute kidney injury (AKI) is a syndrome that frequently affects the critically ill. Recently, an increased number of dinucleotide repeats in the HMOX1 gene were reported... (Observational Study)
Observational Study
Acute kidney injury (AKI) is a syndrome that frequently affects the critically ill. Recently, an increased number of dinucleotide repeats in the HMOX1 gene were reported to associate with development of AKI in cardiac surgery. We aimed to test the replicability of this finding in a Finnish cohort of critically ill septic patients. This multicenter study was part of the national FINNAKI study. We genotyped 300 patients with severe AKI (KDIGO 2 or 3) and 353 controls without AKI (KDIGO 0) for the guanine-thymine (GTn) repeat in the promoter region of the HMOX1 gene. The allele calling was based on the number of repeats, the cut off being 27 repeats in the S-L (short to long) classification, and 27 and 34 repeats for the S-M-L2 (short to medium to very long) classification. The plasma concentrations of heme oxygenase-1 (HO-1) enzyme were measured on admission. The allele distribution in our patients was similar to that published previously, with peaks at 23 and 30 repeats. The S-allele increases AKI risk. An adjusted OR was 1.30 for each S-allele in an additive genetic model (95% CI 1.01-1.66; p = 0.041). Alleles with a repeat number greater than 34 were significantly associated with lower HO-1 concentration (p<0.001). In septic patients, we report an association between a short repeat in HMOX1 and AKI risk.
Topics: Acute Kidney Injury; Aged; Alleles; Cohort Studies; Comorbidity; Critical Illness; Female; Finland; Genetic Predisposition to Disease; Genotype; Heme Oxygenase-1; Humans; Male; Middle Aged; Minisatellite Repeats; Polymorphism, Genetic; Promoter Regions, Genetic; Prospective Studies; Risk Factors; Sepsis
PubMed: 31120979
DOI: 10.1371/journal.pone.0217291 -
Oncotarget Apr 2017MNS16A, a functional polymorphic tandem repeat minisatellite, is located in the promoter region of an antisense transcript of the human telomerase reverse transcriptase...
MNS16A, a functional polymorphic tandem repeat minisatellite, is located in the promoter region of an antisense transcript of the human telomerase reverse transcriptase gene. MNS16A promoter activity depends on the variable number of tandem repeats (VNTR) presenting varying numbers of transcription factor binding sites for GATA binding protein 1. Although MNS16A has been investigated in multiple cancer epidemiology studies with incongruent findings, functional data of only two VNTRs (VNTR-243 and VNTR-302) were available thus far, linking the shorter VNTR to higher promoter activity.For the first time, we investigated promoter activity of all six VNTRs of MNS16A in cell lines of colorectal, lung and prostate cancer using Luciferase reporter assay. In all investigated cell lines shorter VNTRs showed higher promoter activity. While this anticipated indirect linear relationship was affirmed for colorectal cancer SW480 (P = 0.006), a piecewise linear regression model provided significantly better model fit in lung cancer A-427 (P = 6.9 × 10-9) and prostate cancer LNCaP (P = 0.039). In silico search for transcription factor binding sites in MNS16A core repeat element suggested a higher degree of complexity involving X-box binding protein 1, general transcription factor II-I, and glucocorticoid receptor alpha in addition to GATA binding protein 1.Further functional studies in additional cancers are requested to extend our knowledge of MNS16A functionality uncovering potential cancer type-specific differences. Risk alleles may vary in different malignancies and their determination in vitro could be relevant for interpretation of genotype data.
Topics: Binding Sites; Cell Line, Tumor; Colorectal Neoplasms; Female; Gene Expression Regulation, Neoplastic; Genetic Variation; Humans; Lung Neoplasms; Male; Minisatellite Repeats; Polymorphism, Genetic; Promoter Regions, Genetic; Prostatic Neoplasms; Protein Binding; Telomerase; Transcription Factors
PubMed: 28427205
DOI: 10.18632/oncotarget.15884 -
Applied and Environmental Microbiology Sep 2019Due to the potential of enterohemorrhagic (EHEC) serogroup O157 to cause large food borne outbreaks, national and international surveillance is necessary. For... (Comparative Study)
Comparative Study
Due to the potential of enterohemorrhagic (EHEC) serogroup O157 to cause large food borne outbreaks, national and international surveillance is necessary. For developing an effective method of molecular surveillance, a conventional method, multilocus variable-number tandem-repeat analysis (MLVA), and whole-genome sequencing (WGS) analysis were compared. WGS of 369 isolates of EHEC O157 belonging to 7 major MLVA types and their relatives were subjected to comprehensive typing, core genome single nucleotide polymorphism (cgSNP), and core genome multilocus sequence typing (cgMLST) analyses. The typing resolution was the highest in cgSNP analysis. However, determination of the sequence of the mismatch repair protein gene is necessary because spontaneous deletion of the gene could lead to a hypermutator phenotype. MLVA had sufficient typing resolution for a short-term outbreak investigation and had advantages in rapidity and high throughput. cgMLST showed less typing resolution than cgSNP, but it is less time-consuming and does not require as much computer power. Therefore, cgMLST is suitable for comparisons using large data sets (e.g., international comparison using public databases). In conclusion, screening using MLVA followed by cgMLST and cgSNP analyses would provide the highest typing resolution and improve the accuracy and cost-effectiveness of EHEC O157 surveillance. Intensive surveillance for enterohemorrhagic (EHEC) serogroup O157 is important to detect outbreaks and to prevent the spread of the bacterium. Recent advances in sequencing technology made molecular surveillance using whole-genome sequence (WGS) realistic. To develop rapid, high-throughput, and cost-effective typing methods for real-time surveillance, typing resolution of WGS and a conventional typing method, multilocus variable-number tandem-repeat analysis (MLVA), was evaluated. Nation-level systematic comparison of MLVA, core genome single nucleotide polymorphism (cgSNP), and core genome multilocus sequence typing (cgMLST) indicated that a combination of WGS and MLVA is a realistic approach to improve EHEC O157 surveillance.
Topics: Computer Simulation; Disease Outbreaks; Epidemiological Monitoring; Escherichia coli Infections; Escherichia coli O157; Genome, Bacterial; Minisatellite Repeats; Multilocus Sequence Typing; Polymorphism, Single Nucleotide; Whole Genome Sequencing
PubMed: 31227555
DOI: 10.1128/AEM.00728-19