The myeloperoxidase inhibitor mitiperstat (AZD4831) does not prolong the QT interval at expected therapeutic doses.

Mitiperstat is a myeloperoxidase inhibitor in clinical development for treatment of patients with heart failure and preserved or mildly reduced ejection fraction, non-alcoholic steatohepatits and chronic obstructive pulmonary disease. We aimed to assess the risk of QT-interval prolongation with mitiperstat using concentration-QT (C-QT) modeling. Healthy male volunteers were randomized to receive single oral doses of mitiperstat 5, 15, 45, 135, or 405 mg (n = 6 per dose) or matching placebo (n = 10) in a phase 1 study (NCT02712372). Time-matched pharmacokinetic and digital electrocardiogram data were collected at the baseline (pre-dose) and at 11 time-points up to 48 h post-dose. C-QT analysis was prespecified as an exploratory objective. The prespecified linear mixed effects model used baseline-adjusted QT interval corrected for the heart rate by Fridericia's formula (ΔQTcF) as a dependent variable and plasma mitiperstat concentration as an independent variable. Initial exploratory analyses indicated that all model assumptions were met (no effect on heart rate; appropriate use of QTcF; no hysteresis; linear concentration-response relationship). Model-predicted mean baseline-corrected and placebo-adjusted ΔΔQTcF was +0.73 ms (90% confidence interval [CI]: -1.73, +3.19) at the highest anticipated clinical exposure (0.093 µmol/L) during treatment with mitiperstat 5 mg once daily. The upper 90% CI was below the established threshold of regulatory concern. The 16-fold margin to the highest observed exposure was high enough to mean that a positive control was not needed. Mitiperstat is not associated with risk of QT-interval prolongation at expected therapeutic concentrations.

Efficient management of pulmonary embolism diagnosis using a two-step interconnected machine learning model based on electronic health records data.

Pulmonary Embolism (PE) is a life-threatening clinical disease with no specific clinical symptoms and Computed Tomography Angiography (CTA) is used for diagnosis. Clinical decision support scoring systems like Wells and rGeneva based on PE risk factors have been developed to estimate the pre-test probability but are underused, leading to continuous overuse of CTA imaging. This diagnostic study aimed to propose a novel approach for efficient management of PE diagnosis using a two-step interconnected machine learning framework directly by analyzing patients' Electronic Health Records data. First, we performed feature importance analysis according to the result of LightGBM superiority for PE prediction, then four state-of-the-art machine learning methods were applied for PE prediction based on the feature importance results, enabling swift and accurate pre-test diagnosis. Throughout the study patients' data from different departments were collected from Sina educational hospital, affiliated with the Tehran University of medical sciences in Iran. Generally, the Ridge classification method obtained the best performance with an F1 score of 0.96. Extensive experimental findings showed the effectiveness and simplicity of this diagnostic process of PE in comparison with the existing scoring systems. The main strength of this approach centered on PE disease management procedures, which would reduce avoidable invasive CTA imaging and be applied as a primary prognosis of PE, hence assisting the healthcare system, clinicians, and patients by reducing costs and promoting treatment quality and patient satisfaction.

The U-wave: A remaining enigma of the electrocardiogram.

The U-wave's electrophysiological origin remains unknown and is subject to debate. It is rarely used for diagnosis in clinical practice. The aim of this study was to review new information regarding the U-wave. Further to present the proposed theories behind the U-wave's origin along with potential pathophysiologic and prognostic implications related to its presence, polarity and morphology. METHOD: Literature searches were conducted to retrieve publications related to the electrocardiogram U-wave in the literature database Embase. RESULTS: The review of the literature revealed the following major theories that will be discussed; late depolarisation, delayed or prolonged repolarisation, electro-mechanical stretch and IK1 dependent intrinsic potential differences in the terminal part of the action potential. Various pathologic conditions were found to correlate with the presence and properties of the U-wave, such as its amplitude and polarity. Abnormal U-waves can, for example, be observed in coronary artery disease with ongoing myocardial ischemia or infarction, ventricular hypertrophy, congenital heart disease, primary cardiomyopathy and valvular defects. Negative U-waves are highly specific for the presence of heart diseases. Concordantly negative T- and U-waves are especially associated with cardiac disease. Patients with negative U-waves tend to have higher blood pressure and history of hypertension, higher heart rate, cardiac disease and left ventricular hypertrophy compared to subjects with normal U-waves. Negative U-waves have been found to be associated with increased risk of all-cause mortality, cardiac death and cardiac hospitalisation in men. CONCLUSIONS: The origin of the U-wave is still not established. U-wave diagnostics may reveal cardiac disorders and the cardiovascular prognosis. Including the U-wave characteristics in the clinical ECG assessment may be useful.

Automated analysis of karyotype images.

Karyotype is a genetic test that is used for detection of chromosomal defects. In a karyotype test, an image is captured from chromosomes during the cell division. The captured images are then analyzed by cytogeneticists in order to detect possible chromosomal defects. In this paper, we have proposed an automated pipeline for analysis of karyotype images. There are three main steps for karyotype image analysis: image enhancement, image segmentation and chromosome classification. In this paper, we have proposed a novel chromosome segmentation algorithm to decompose overlapped chromosomes. We have also proposed a CNN-based classifier which outperforms all the existing classifiers. Our classifier is trained by a dataset of about 1,62,000 human chromosome images. We also introduced a novel post-processing algorithm which improves the classification results. The success rate of our segmentation algorithm is 95%. In addition, our experimental results show that the accuracy of our classifier for human chromosomes is 92.63% and our novel post-processing algorithm increases the classification results to 94%.

AZD8233 antisense oligonucleotide targeting PCSK9 does not prolong QT interval.

AIMS: AZD8233 is a proprotein convertase subtilisin/kexin type 9 (PCSK9) antisense oligonucleotide under development for treatment of hypercholesterolaemia. A prespecified concentration-QT analysis was performed based on data from a single ascending dose study that was prospectively designed to act as a TQT study substitute. METHODS: Subcutaneous single doses ranging from 4 to 120 mg were evaluated in 73 adult healthy male subjects. Time-matched 12-lead digital ECG and plasma concentrations (n = 15) were measured at baseline and up to 48 hours after dose in each subject. The analysis was performed using a linear mixed effect model, where change from baseline QTc (ΔQTc) was a dependent variable and time-matched AZD8233 concentration was an independent variable. RESULTS: The high clinical exposure scenario was defined as 1.7-fold the expected Cmax following an assumed therapeutic dose of 60 mg, which corresponds to AZD8233 plasma concentration of 1.39 µg/mL. Estimated placebo-corrected and baseline-adjusted QTcF interval (ΔΔQTcF) at this concentration was -2.2 ms (90% CI: -4.11, -0.28). Furthermore, the upper 90% ΔΔQTcF confidence interval was estimated to be below 10 ms at all observed concentrations. CONCLUSION: As the effect on ΔΔQTcF is below the threshold for regulatory concern (10 ms), it can be concluded that AZD8233 does not induce QTcF prolongation at the high clinical exposure scenario.

Development of a multifunctional system based on CoFe2O4@polyacrylic acid NPs conjugated to folic acid and loaded with doxorubicin for cancer theranostics.

In this work, a multifunctional theranostic nanocomposite based on CoFe2O4@polyacrylic acid (PAA)-Folic Acid (FA) Doxorubicin (Dox)loadNPs was designed for the multifunctional cancer treatment. Several techniques such as TEM, DLS,ζ-potential, vibrating sample magnetometer, XRD, and UV-Vis spectrophotometer were applied for investigating physicochemical properties of the nanosystem. The percentage of the loaded drug, loading efficiency,in vitrorelease (pH 5.4 and 7.4),invitroMRI measurements, and MTT assay (4T1 and 9A9 cell lines) were evaluated. Results showed that the percentage of loaded drug and loading efficiency was 53.33 ± 3.5 and 80.00 ± 5.3%, respectively, showing the system's high ability for Dox encapsulation. Release study showed that Dox loaded in the CoFe2O4@PAA-FA(Dox)loadNPs released faster at pH 5.4 than pH 7.4.In vitro, MRI measurements confirmed that CoFe2O4@PAA NPs could be used as a contrast agent in MRI measurements withr2 = 18.2 mM-1s-1. MTT assay demonstrated the biocompatibility of NPs, also showed a more efficient therapeutic effect for CoFe2O4@PAA-FA(Dox)loadNPs than free Dox and CoFe2O4@PAA(Dox)loadNPs.

A Rare Mutation in the MARVELD2 Gene Can Cause Nonsyndromic Hearing Loss.

The MARVELD2 gene which is located on the 5q13.2 may cause nonsyndromic hearing loss (NSHL) with autosomal recessive inherited pattern. So far c.1331+1G>A (IVS4+1G>A); NM_001038603.3, variant in deafness, has only reported previously in one Pakistani family in 2008 and it is reported for the first time in Iran and second time in the world. The case is a 21-year-old Iranian woman who has NSHL referred for genetic consultation, and her parents had a consanguineous marriage. To study the responsible genes for the mentioned disorder, whole exome sequencing (WES) was performed for the case. The result of WES analysis revealed a transition at the splice donor variant site of the MARVELD2 gene. The NGS result was confirmed by Sanger sequencing.

Drug-induced myocardial dysfunction - recommendations for assessment in clinical and pre-clinical studies.

Introduction: Drug-induced myocardial dysfunction is an important safety concern during drug development. Oncology compounds can cause myocardial dysfunction, leading to decreased left ventricular ejection fraction and heart failure via several mechanisms. Cardiovascular imaging has a major role in the early detection and monitoring of cardiotoxicity. Echocardiography is the method of choice because of its widespread availability, low cost, and absence of radiation exposure. Cardiac magnetic resonance imaging can provide better reliability, reproducibility, and accuracy in the detection of drug-induced myocardial dysfunction. In addition, it enables assessment of myocardial edema, fibrosis, and necrosis. Cardiac serologic biomarkers such as troponins and B-type natriuretic peptides are used in combination with imaging during drug development. This article provides a general overview of each imaging modality and practical guidance for early detection and monitoring of cardiotoxicity.Areas covered: Cardiovascular imaging modalities and cardiac biomarkers for monitoring of cardiac function and early detection of drug-induced myocardial dysfunction in drug development.Expert opinion: Some new drugs especially in the oncology field, can cause myocardial dysfunction. Depending on the strength of pre-clinical or clinical data, CV imaging modalities and cardiac biomarkers play an important role in the early detection and mitigation plans for such drugs during their development.

Highly Sensitive Determination of Bisphenol A in Bottled Water Samples by HPLC after Its Extraction by a Novel Th-MOF Pipette-Tip Micro-SPE.

In this study, a novel thorium metal organic framework was synthesized, characterized and used as a sorbent for very efficient pipette tip micro solid-phase extraction of bisphenol A in bottled drinking water samples using high-performance liquid chromatography as detecting instrument. Parameters which influence extraction efficiency such as pH, sample volume, amount of sorbent, type and volume of eluent, number of aspirating and dispensing cycles for extraction and elution, and volume of the sample solution were studied and optimized. A linear calibration curve was obtained in the range of 0.002-0.456 ng mL-1 (r2 = 0.996) with a detection limit of 0.0010 ng mL-1. Repeatability of batch-to-batch extraction was better than 5.0% and a reproducibility of 3.2% for real samples obtained.

Amendment of Caulerpa sertularioides marine alga with sulfur-containing materials to accelerate Cu removal from aqueous media.

This study reports a new approach of alga amendment in a live mode. The Caulerpa sertularioides alga was modified with sulfur-containing materials of methionine (C5H11NO2S) and sodium sulfate (Na2SO4) to more concentrate the sulfur content of the yielded biomass (adsorbent). The simple and amended C. sertularioides alga was fully characterized with FTIR, SEM, EDX, BET, BJH, and pHzpc techniques. The copper adsorption from aqueous media was done by three adsorbents of C. sertularioides-simple (CSS), C. sertularioides-Na2SO4 (CSN), and C. sertularioides-C5H11NO2S (CSC). The parameters of pH (2-6), adsorbent dosage (2-10 g/L), and contact time (3-80 min) were optimized at 5, 5 g/L, and 60 min, respectively. According to Langmuir isotherm (the best-fitted model), the maximum adsorption capacity of CSN (98.04 mg/g) was obtained 2.4 times higher than CSC (40.73 mg/g) and 9.5 times higher than CSS (10.29 mg/g). The Cu adsorption process by the adsorbents was best-fitted pseudo-second-order kinetic model. The CSN, CSC, and CSS biomasses were successfully reused 5, 4, and 4 times, respectively. The thermodynamic study revealed that the copper adsorption process by CSN is exothermic and non-spontaneous. Finally, the suitability of adsorbents prepared from algae was tested by cleaning a simulated wastewater.

Ultrasound assisted reverse micelle efficient synthesis of new Ta-MOF@ Fe3O4 core/shell nanostructures as a novel candidate for lipase immobilization.

In the present study, Ta-MOF@Fe3O4 core/shell nanostructures were synthesized in optimal conditions using the rapid, efficient, and novel ultrasound assisted reverse micelle method. FTIR, TGA/DTG, XRD, TEM, EDS and N2 adsorption/desorption isotherms were conducted in order to obtain samples with desirable properties. Results showed that the synthesized products had the thermal stability of 200 °C, particle-size distribution of 38 nm and surface area of 740 m2/g. Also, the VSM test showed that these compounds have desirable magnetic properties which provide the opportunity for recovery. Based on these obtained properties, final products were used as a novel candidate for enzyme immobilization. Results of SEM images revealed that the Bacillus licheniformis Km12 lipase is efficiently loaded on the Ta-MOF@Fe3O4 core/shell substrate. The stability test indicated the high stability of the enzyme loaded into these nanostructures. The synthesis method and the results obtained from enzyme immobilization developed in this study can be a new strategy for various applications of these novel compounds in diverse biological fields.

Fabrication of a new superparamagnetic metal-organic framework with core-shell nanocomposite structures: Characterization, biocompatibility, and drug release study.

The Superparamagnetic CoFe2O4NPs@Mn-Organic Framework core-shell nanocomposites that had potential application in targeted drug-delivery were synthesized by layer to layer method. The structure and composition of the obtained microspheres were characterized by SEM, TEM, DLS, XRD, VSM, FTIR, and TG analysis. Results showed that the structures have a high degree crystalline, high temperature stability, magnetics and core-shell nanocomposites. Therefore, it is an excellent candidate for drug delivery systems. Afterwards, Daunorubicin (as a drug model) was laden in the MOFs by a Simple stirring. For comparison of magnetic properties of MOFs for drug delivery, an external magnetic field applied to the plate to evaluate the efficiency. The external magnetic field significantly increases anti-tumor activity of formulation (drug+ MOFs). The results showed that MOFs are biocompatible, which endue MOFs great potential in targeting drug-delivery systems with enhanced efficiency.

The role of epidermal growth factor receptor (EGFR) common gene mutations in Iranian women with uterine fibroids.

OBJECTIVE: Uterine myomas are benign uterine tumors that originate from smooth muscle cells of the myometrium. This common complication can be associated with irreversible complications, including infertility and malignancy. Better understanding of the genetic characteristics of myoma may effect on treatment. Epidermal growth factor receptor gene (EGFR) is one of the most important genes that has the major role in the pathogenesis of myoma, cell growth, differentiation, proliferation and mutagenesis. The aim of this study was to investigate EGFR common gene mutations in Iranian women with uterine fibroids. METHODS: In this case-control study, Common EGFR gene mutations in exons 21 and exons 19 of 100 women with uterine leiomyoma as cases and 100 healthy women as controls were studied. To investigate deletion mutations of exon 19 (rs121913438) and point mutations of exon 21 (rs121434568), Tetra ARMS/PCR, ARMS and conventional PCR methods were used respectively and the results were analyzed using χ 2 test. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression with control for age. RESULT: Our results showed significant difference in genotypes frequency of (TT, TG, GG) for exon 21 and (WW, WD, DD) of exon 19 among cases and controls (P-Value = 5.672e-20) and (P-Value = 3.242e-15). There was a significant relationship between [G] allele and risk uterine myoma (P-Value = 3.018e-36) and the presence of [G] allele increased the chance of developing the disease OR = 0.004, 95% CI 0.001-0.013. The result also showed significant relationship between [D] allele and risk of uterine myoma (P-Value = 1.324e-15). In addition, presence of [D] allele, increased the chance of developing the disease (OR = 0.008, 95% C.I. = 0.002-0.033). CONCLUSION: The results indicated a significant correlation between mutations in exon 19 (rs121913438) and exon 21(rs121434568) of EGFR gene and susceptibility of myoma in the study population.

The Association of rs1670533 Polymorphism in RNF212 Gene With the Risk of Down Syndrome in Young Women.

Objective: To evaluate association between polymorphism rs1670533 in RNF212 gene with the risk of Down syndrome in young women. Materials and methods: In a case control study, one hundred pregnant women were evaluated in both group. The case group consisted pregnancy with diagnosis of Down syndrome in women younger than 35 years old. The control group consisted pregnancy with normal neonate. Fifty pregnant women in each group were allocated.one hundred blood samples were collected. Genomic DNA was extracted by salting - out method and polymorphism of rs1670533 were detected by PCR.PCR products were detected on 2% agarose gel electrophoresis. Results: The TTrs1670533 haplotype was present in 36% of pregnant women with Down syndrome versus 14% of normal pregnant women, (p = 0.003 e-12; CI 95%1.665-5.305, OR = 3.107); TC haplotype was present in 56% of normal pregnancy regarding of16% of pregnancy with Down syndrome (p = 4.288 e = 12; CI 95%: 0.145-0.25; OR = 0.126). Conclusion: It seems that TTrs1670533 haplotype is a risk factor for pregnancy with Down syndrome in young women and TC haplotype has protective effect.

Aldosterone to Renin Ratio as a Screening Instrument for Primary Aldosteronism in a Middle-Aged Population with Atrial Fibrillation.

Atrial fibrillation seems to be overrepresented among patients with primary aldosteronism. The aim of this study was to determine the usefulness of aldosterone to renin ratio as a screening instrument for primary aldosteronism in an atrial fibrillation population with relatively low cardiovascular risk profile. A total of 149 patients <65 years and with history of AF were screened for primary aldosteronism using aldosterone to renin ratio. Pathologically increased aldosterone to renin ratio (>65 pmol/mIU) was found in 15 participants (10.1%). Further investigation of the positive screened participants and confirmatory saline infusion test resulted in a diagnosis of primary aldosteronism in four individuals out of 149 (2.6%). Three out of the four individuals with primary aldosteronism had previously been diagnosed with hypertension, but only one out of the four had uncontrolled blood pressure, that is, >140/90 mmHg. All participants had normal potassium levels. Individuals with increased aldosterone to renin ratio had significantly higher mean systolic and diastolic blood pressure in comparison to participants with normal aldosterone to renin ratio (136 vs. 126 mmHg, p=0.02 and 84 vs. 78 mmHg, p=0.02). These findings suggest that assessment of aldosterone to renin ratio can be useful for identification of underlying primary aldosteronism in patients with diagnosed atrial fibrillation and hypertension in spite of well controlled blood pressure and normokalemia.

Rationale and Design of a Genetic Study on Cardiometabolic Risk Factors: Protocol for the Tehran Cardiometabolic Genetic Study (TCGS).

BACKGROUND: Cardiometabolic risk factors comprise cardiovascular diseases and/or diabetes, and need to be evaluated in different fields. OBJECTIVE: The primary aim of the Tehran Cardiometabolic Genetic Study (TCGS) is to create a comprehensive genome-wide database of at least 16,000 Tehranians, who are participants of the ongoing Tehran Lipid and Glucose Study (TLGS) cohort. METHODS: TCGS was designed in collaboration with the Research Institute for Endocrine Sciences and the genetic company deCODE. Participants had already been followed for over a 20-year period for major cardiometabolic-related health events including myocardial infarction, stroke, diabetes mellitus, hypertension, obesity, hyperlipidemia, and familial hypercholesterolemia. RESULTS: The TCGS cohort described here comprises 17,186 (86.3%) of the 19,905 TLGS participants who provided a baseline blood sample that was adequate for plasma and deoxyribonucleic acid analysis. This study is comprised of 849 individuals and 3109 families with at least one member having genotype information. Finally, 5977 males and 7422 females with the total genotyping rate of 0.9854 were genotyped with HumanOmniExpress-24-v1-0 bead chips (containing 649,932 single-nucleotide polymorphism loci with an average mean distance of 4 kilobases). CONCLUSIONS: Investigations conducted within the TCGS will seek to identify relevant patterns of genetic polymorphisms that could be related to cardiometabolic risk factors in participants from Tehran. By linking genome-wide data to the existing databank of TLGS participants, which includes comprehensive behavioral, biochemical, and clinical data on each participant since cohort inception in 1999, the TCGS will also allow exploration of gene-gene and gene-environment interactions as they relate to disease status.

Relationship Between Some Single-nucleotide Polymorphism and Response to Hydroxyurea Therapy in Iranian Patients With ß-Thalassemia Intermedia.

OBJECTIVE: To evaluate the possible relationship between hydroxyurea (HU) response and some single-nucleotide polymorphism (SNP) in patients affected by ß-thalassemia intermedia. MATERIALS AND METHODS: In this cross-sectional study, 100 ß-thalassemia intermedia patients who were taking HU with a dose of 8 to 15 mg/kg body weight per day for a period of at least 6 months were randomly selected between February 2013 and October 2014 in southern Iran. HU response was defined based on decrease or cessation of the blood transfusion need and evaluation of Hb level. RESULTS: In univariate analysis, from all evaluated SNPs, only rs10837814 SNP of olfactory receptors (ORs) OR51B2 showed a significant association with HU response (P=0.038) and from laboratory characteristics, only nucleated red blood cells showed significant associations (116%±183%) in good responders versus (264%±286%) in poor responders (P=0.045). In multiple logistic regression, neither laboratory variables nor different SNPs, showed significant association with HU response. Three novel nucleotide variations (-665 [A→C], -1301 [T→G],-1199 delA) in OR51B2 gene were found in good responders. CONCLUSIONS: None of the evaluated SNPs in our study showed significant association with HU response. Further larger studies and evaluation of other genes are suggested.

Drug-induced blood pressure increase - recommendations for assessment in clinical and non-clinical studies.

INTRODUCTION: Changes in blood pressure (BP) are now proactively examined throughout the drug development process as an integral aspect of safety monitoring. This is because hypertension is a very strong risk factor for cardiovascular events and drug-induced increases in BP have attracted increased regulatory attention. However, there is currently no guidance from regulatory agencies on the minimum BP data required for submissions, and there are no specific criteria for what constitutes a safety signal for increased BP in non clinical studies. Areas covered: Evaluation of BP increases through the drug discovery and development process. Expert opinion: Research into the effects of drugs should begin before clinical development is initiated and continue throughout the clinical trial program. Non clinical studies should inform a benefit-risk analysis that will aid decision-making of whether to enter the drug into Phase I development. The degree of acceptable risk will vary according to the therapy area, treatment indication and intended population for the new drug, and the approach to BP assessment and risk mitigation should be tailored accordingly. However, BP monitoring should always be included in clinical trials, and data collected from multiple studies, to convincingly prove or refute a suspicion of BP effects.

A novel deletion and two recurrent substitutions on type VII collagen gene in seven Iranian patients with epidermolysis bullosa.

OBJECTIVES: Epidermolysis bullosa is one of the most important series of mechano-bullous heritable skin disorders which is categorized into four major types according to the layer that bullae forms within basement membrane zone. In dystrophic form of the disease, blisters are made in the sublamina densa zone, at the level of type VII collagen protein which produce anchoring fibrils. Type VII collagen gene is the only responsible gene for this form. The aim of this study was to survey causative mutations of type VII collagen gene among Iranian patients with epidermolysis bullosa. MATERIALS AND METHODS: For this purpose, exons 73-75 were investigated by polymerase chain reaction followed by direct sequencing. RESULTS: In current study, we found three different point mutations in type VII collagen alleles in 7 out of 50 patients. Four patients were homozygous for a new deletion which resulted in frame shift (p.Pro2089fs). Two patients were homozygous for a recurrent glycine substitution (p.G2031S) and one patient was detected with an allele carrying a substitution (p.R2069C). CONCLUSION: The results emphasized heterogeneity in the type VII collagen gene and will provide a sign for early diagnosis and future study of the disease pathogenesis.

Association of Mycobacterium infections in patients with Mendelian susceptibility to mycobacterial disease with venous thromboembolism.

An association between a hypercoagulable state and Mendelian susceptibility to mycobacterial disease (MSMD) has been established in a few studies; resultant thrombosis is considered rare. In a case-control study, the prevalence of factor V Leiden, prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C mutations were investigated in mycobacterium-infected patients. The study comprised 30 patients with mycobacterial infections (invasive, disseminated and/or recurrent infections with Bacille Calmette-Guerin or non-tuberculosis mycobacteria and Mycobacterium Tuberculosis with positive results for acid-fast bacilli and tuberculin skin tests) and 30 normal healthy controls. Forty female (66.7%) and 20 male subjects (33.3%) aged from 3 to 70 years were recruited into this study. Genotyping of targeted genes was performed by RT-PCR and cytokine TNF-α concentrations were quantified using a commercially available ELISA kit. Significant associations between mycobacterial infection and TNF-α production after stimulating peripheral blood mononuclear cells with LPS alone and with IFN-γ plus LPS were identified. Moreover, genotyping analysis in the studied population revealed a significant association between MTHFR c.677C>T (OR, 3.28; 95% CI, 1.35-7.92; P < 0.05), MTHFR c.1298A>C (OR, 2.33; 95% CI, 1.10-4.93; P < 0.05) and mycobacterial infection in affected patients, indicating susceptibility to venous thromboembolism according to previous studies. Additionally, mycobacterium-infected patients had a significantly greater prevalence of MTHFR C677T and A1298C mutations than controls.