Search Results (46)

COVID-19 not only affects the respiratory system but also increases the risk of cerebrovascular complications, including ischemic stroke. Experimental and clinical data suggest that cytokine dysregulation and polymorphisms of thrombophilia-related genes (MTHFR, MTR, and MTRR) may jointly promote hypercoagulation, endothelial dysfunction, and thromboinflammation, thereby contributing to post-COVID ischemic stroke. This study included 160 patients treated at Zangiota Infectious Diseases Hospitals (2021–2023): 60 patients with ischemic stroke in the acute or post-COVID period (experiment group), 50 COVID-19 patients without ischemic stroke (comparison group), and 50 ischemic stroke patients without COVID-19 (control group). Clinical–neurological and immunological parameters were assessed, and polymorphisms in thrombophilia/folate cycle genes (MTHFR C677T, MTR, and MTRR) were genotyped by PCR/real-time PCR. Statistical analysis included χ² tests, t-tests, logistic regression with odds ratios (OR) and 95% confidence intervals (CI); Hardy–Weinberg equilibrium was verified. A strong association was identified between the MTHFR C677T polymorphism and ischemic stroke on the background of COVID-19 (OR = 5.4; 95% CI: 2.1–13.8; p < 0.001). The TNF-α rs1800629 polymorphism was also significantly associated with COVID-19-related cerebrovascular events (OR = 3.27; 95% CI: 1.4–7.6; p = 0.006). Carriage of two or more minor alleles produced a synergistic effect, markedly increasing the risk of post-COVID ischemic stroke (OR = 5.59; 95% CI: 2.3–13.6; p < 0.001). These polymorphisms were linked to hyperhomocysteinemia, endothelial dysfunction, and mechanisms contributing to multifactorial arterial ischemic events. The combined assessment of thrombophilia and folate cycle-related genotypes and clinical indicators may provide a potential framework for improved risk stratification. Polymorphisms in MTHFR may appear to represent important genetic determinants of ischemic stroke following COVID-19, particularly in the context of arterial ischemic mechanisms. Full article

The multiple-transferable resistance protein (MtrR) is a transcriptional repressor of the mtrCDE-encoded drug efflux pump and Type IV pilus biosynthesis (pilM), and an activator of penicillin-binding protein 1 (ponA) expression in Neisseria gonorrhoeae. Previously published microarray data suggested that MtrR is also an activator of ltgA expression in the gonococcus. LtgA is a lytic transglycosylase responsible for approximately half of recycled peptidoglycan fragments and released peptidoglycan-derived cytotoxins, which cause ciliary damage and induce specific inflammatory responses. The fragments generated by LtgA during peptidoglycan remodeling can either be recognized by the permease AmpG for uptake into the bacterial cytoplasm and recycled for new cell wall growth and general metabolism or released into the external milieu. Therefore, we sought to define the capacity of MtrR to regulate LtgA expression in gonococci. We show that MtrR binds to the ltgA promoter region in a concentration-dependent manner, and that this binding results both in increased ltgA mRNA transcription and LtgA protein levels during exponential growth. Deletion of mtrR in N. gonorrhoeae decreased peptidoglycan monomer release from growing cells and increased autolysis. These results suggest that MtrR regulation of ltgA impacts peptidoglycan-derived cytotoxin release and autolysis in the gonococcus. This study suggests a central role of MtrR in coordinating aspects of the cellular envelope that may contribute to gonococcal pathogenesis. Full article

We investigated whether antipsychotic treatment response was influenced by the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR), and A66G of methyltetrahydrofolate–homocysteine methyltransferase reductase (MTRR)—genes central to folate and homocysteine metabolism and methylation, pathways often altered in schizophrenia patients. To our knowledge, no study has examined associations of C677T and A1298C with changes in schizophrenia symptom severity after antipsychotic treatment, while studies on metabolic outcomes remain sparse and inconsistent. The MTRR A66G has been assessed only once for metabolic parameters—not symptom severity—and sex-stratified analyses are lacking for all polymorphisms. A total of 186 antipsychotic-naïve first-episode or nonadherent chronic psychosis patients and 242 controls were genotyped using PCR-RFLP. Clinical assessments—including Positive and Negative Syndrome Scale (PANSS) scores, PANSS factor scores, and metabolic parameters (fasting plasma lipids and glucose levels, and body mass index)—were conducted at baseline and after 8 weeks. Genotype and allele frequencies did not differ between patients and controls. Significant associations emerged only for symptom changes, specifically within PANSS factor domains, in a sex-dependent manner. Female MTHFR 1298-A allele carriers (AA and AC) showed greater improvement in PANSS negative factor scores, whereas male MTRR 66-G allele carriers (GG and AG) showed reduced improvement in PANSS cognitive factor scores. Effect sizes were strong to very strong, with relatively modest contributions. MTHFR A1298C and MTRR A66G have sex-dependent impacts on symptomatic improvement—but not metabolic outcomes—after antipsychotic treatment. Accordingly, folate–homocysteine genetic markers and sex-specific factors can guide the development of personalized antipsychotic treatment approaches. Full article

Background/Objectives: The escalating threat of drug-resistant Neisseria gonorrhoeae underscores the urgent need for novel therapeutic agents. Zoliflodacin, a first-in-class spiropyrimidinetrione antibiotic that targets bacterial DNA gyrase and topoisomerase IV, represents a promising candidate for gonorrhea treatment. Methods: From 2020 to 2023, a total of 876 urogenital N. gonorrhoeae isolates were collected from 35 hospitals across Shanghai, China. In vitro susceptibilities to zoliflodacin and six conventional antibiotics (penicillin, tetracycline, ciprofloxacin, azithromycin, ceftriaxone, and spectinomycin) were determined using the agar dilution method. Whole-genome sequencing was conducted to identify sequence types (STs) and amino-acid substitutions in GyrA, GyrB, ParC, ParE, and MtrR. Results: Zoliflodacin exhibited potent in vitro activity, with minimum inhibitory concentrations (MICs) ranging from ≤0.004 to 0.25 mg/L (MIC₅₀ = 0.06 mg/L; MIC₉₀ = 0.125 mg/L), all below the breakpoint (0.5 mg/L). Notably, zoliflodacin maintained high activity against isolates resistant to ceftriaxone, azithromycin, ciprofloxacin, penicillin, and tetracycline. Although all isolates were susceptible to zoliflodacin, elevated MIC values were observed in ST7363 and ST8123 compared with other clones. Genomic analysis identified no substitutions associated with increased zoliflodacin MICs, and most GyrB sequences, the key gene associated with zoliflodacin resistance, remained intact. Conclusions: These findings demonstrate that zoliflodacin possesses robust activity against circulating multidrug-resistant N. gonorrhoeae lineages in Shanghai and support its potential clinical use for the treatment of gonorrhea. Continued genomic and phenotypic surveillance is warranted to preserve the long-term efficacy of this novel agent. Full article

Background: Recurrent pregnancy loss (RPL) is a multifactorial condition in which genetic variants associated with thrombophilia may contribute to altered coagulation and adverse pregnancy outcomes. Objective: This study aimed to investigate the association between thrombophilia-related single nucleotide variants (SNVs) and coagulation-related metabolites in a cohort of Mexican women with RPL. Methods: A retrospective and descriptive design was conducted including 105 women with at least two consecutive miscarriages and with a multidisciplinary approach that included a thrombophilia-associated SNVs panel. Peripheral blood samples were collected after fasting for biochemical and molecular analyses. Genotyping of thrombophilia-associated SNVs was performed using real-time PCR with custom-designed TaqMan probes on a Rotor-Gene Q platform, including variants in AGT (rs4762, rs699), F7 (rs6046), FGB (rs1800790), MTR (rs1805087), MTRR (rs1801394), MTHFR (rs1801133, rs1801131), F2 (rs1799963), F5 (rs6025), SERPINE1 (rs1799889), F12 (rs1801020), and F13A1 (rs5985) genes. Coagulation parameters evaluated were folic acid, cobalamin, fibrinogen, D-dimer, homocysteine, antithrombin III activity, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), and Factor XII activity. Results: Significant differences were found in INR values across F7-rs6046 genotypes (p = 0.006), with an additive model showing a mean difference of 0.05 (p = 0.0009). The F12-rs1801020 variant was strongly associated with Factor XII activity (p = 0.002) and aPTT (p = 0.045). Conclusions: These findings indicate that F7-rs6046 and F12-rs1801020 genotypes influence specific coagulation parameters, suggesting that certain thrombophilia-associated SNVs may modulate the hemostatic profile in Mexican women with RPL and contribute to personalized risk assessment in reproductive medicine. Full article

Hypothyroidism is a multifactorial endocrine disorder where genetic predisposition plays a significant role. The MTHFR, MTRR, and MTR genes influence thyroid hormone regulation via homocysteine remethylation and DNA methylation. This study examined associations between hypothyroidism and polymorphisms in MTHFR (C677T–rs1801133, A1298C–rs1801131), MTRR (A66G–rs1801394), and MTR (A2756G–rs1805087) genes. Eighty-six patients with hypothyroidism and 87 healthy controls were included. Genotyping was performed using PCR-RFLP. Post hoc analysis confirmed adequate statistical power (95% for MTRR A66G, 84.6% for MTR A2756G). The study adhered to STROBE guidelines. MTHFR polymorphisms showed no significant association when considered individually. However, the MTRR A66G AA genotype was significantly more frequent in patients and conferred a markedly increased disease risk (OR: 4.373; 95% CI: 2.174–8.797; p < 0.001), while the MTR A2756G AG genotype was also more prevalent among patients and associated with higher susceptibility (OR: 2.178; 95% CI: 1.156–4.104; p = 0.008). Genotype combination analysis revealed that CT–AA (OR = 6.898; 95% CI: 1.941–24.516; p = 0.001) and AG–AA (OR = 6.892; 95% CI: 1.494–31.797; p = 0.007) conferred high risk. Certain genotypes correlated with clinical features, including hypercholesterolemia, diabetes, and cardiovascular disease. MTRR A66G and MTR A2756G polymorphisms are associated with hypothyroidism and metabolic comorbidities, both individually and in genotype combinations. These findings underscore the value of multilocus genetic models for understanding thyroid disorders and support the potential role of genetic biomarkers in personalized risk assessment and early diagnosis. GRS analysis demonstrated that each additional risk allele increased hypothyroidism risk (OR = 1.58; 95% CI: 1.18–2.10; p = 0.0018), and the total score showed moderate predictive power (AUC = 0.665; p < 0.001). Full article

Background/Objectives: Subnormal folate levels have a detrimental impact on the growth and development of preschoolers. We aimed to investigate the association between independent/synergistic effects of the gene polymorphisms (methyltetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms, alongside methionine synthase reductase (MTRR) A66G polymorphism and the methionine synthase (MTR) A2756G polymorphism) and serum folate levels as well as cognitive levels in Chinese preschoolers aged 5–7 years. Methods: Data were sourced from 614 children, acquired through the “Long-term Health Effects Assessment Project of Infants and Toddlers Nutritional Pack (LHEAITNP)” program were used. Folate serum concentrations were measured using a microbiologically modified technique. The genotypes of MTHFR A1298C and C677T, together with MTRR A66G, were identified by Kramer’s Allele-Specific PCR (KASP) technique. The cognitive scores of children were assessed by questionnaire. Results: MTHFR 677TT and MTR 2756AG + GG correlated negatively with serum folate levels (TT vs. CC + CT, p = 0.0009 and AG + GG vs. AA, p = 0.0057, respectively). MTHFR C677T and A1298C were independently linked to an elevated risk of suboptimal cognitive development (TT vs. CC + CT, p = 0.0009 and AA vs. CA + CC, p < 0.0001, respectively). The joint impact of these risk genotypes showed significantly increased risk of folate deficiency and inferior cognitive function compared to non-risk genotypes, particularly in those with more than two risk genotypes. The findings were corroborated by a cumulative effects model (p < 0.05). Conclusions: Our results indicate the substantial association between folate-homocysteine metabolism gene variants and serum folate status/cognitive performance in Chinese preschoolers. Potential gene-nutrient interactions worthy of longitudinal investigation. Full article

Background: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is an escalating global health challenge, affecting over 82 million individuals each year. The increasing resistance to commonly used antibiotics such as azithromycin, ciprofloxacin, and cefixime hinders timely and effective treatment, primarily due to the delayed detection of resistant strains. Methods: To overcome these limitations, a hybrid machine learning (ML) and deep learning (DL) framework was developed using a dataset comprising 3786 N. gonorrhoeae isolates. The dataset included clinical metadata and phenotypic resistance profiles. The preprocessing steps involved handling 23% data sparsity, imputing 31 skewed columns, and applying resampling and harmonisation techniques sensitive to data skewness. A predictive pipeline was constructed using both clinical variables and genomic unitigs, and a suite of 33 classifiers was evaluated. Results: The CatBoost model emerged as the top-performing ML algorithm, particularly due to its proficiency in handling categorical data, while a three-layered neural network served as the DL baseline. The ML models outperformed genome-wide association study (GWAS) benchmarks, achieving AUC scores of 0.97 (ciprofloxacin), 0.95 (cefixime), and 0.94 (azithromycin), representing a 4–7% improvement. SHAP analysis identified biologically relevant resistance markers, such as penA mosaic alleles and mtrR promoter mutations, validating the interpretability of the model. Conclusions: The study highlights the potential of ML-driven approaches to enhance the real-time prediction of antimicrobial resistance in N. gonorrhoeae. These methods can significantly contribute to antibiotic stewardship programs, although further validation is required in low-resource settings to confirm their generalisability and robustness across diverse populations. Full article

Purpose: Homocysteine (HCY) metabolism is regulated by the methionine cycle, which is essential for DNA methylation and is associated with the folate cycle. This study examines the alterations in DNA methylation signature including epigenetic age changes, measure cell-free DNA (cfDNA), and HCY concentrations, and identifies genetic markers that may influence homocysteine response following folic acid (FA) supplementation in individuals with hyperhomocysteinemia (HHC). Methods: Blood samples were obtained from 43 HHC patients undergoing FA supplementation. We quantified FA and HCY levels, separated plasma and white blood cell fractions, and evaluated global DNA methylation using LINE-1 bisulfite pyrosequencing. Biological age was determined using Illumina BeadArray technology, and whole-exome sequencing was performed to investigate the patients’ genetic backgrounds. Results: Following FA supplementation, cfDNA levels significantly decreased and correlated positively with HCY (r = 0.2375). Elevated average LINE-1 methylation of cfDNA and PBMC-origin DNA was observed, with mean relative changes of 1.9% for both sample types. Regarding HCY levels, we categorized patients based on their response to FA supplementation. FA responders showed decreased HCY from 15.7 ± 5.5 to 11 ± 2.9 µmol/L, while in FA non-responders, an opposite trend was detected. The average biological age was reduced by 2.6 years, with a notable reduction observed in 80% of non-responders and 48% of responders. Sequencing identified mutations in several genes related to the one-carbon cycle, including MTRR, CHAT, and MTHFD1, with strong correlations to the non-responder phenotypes found in genes like PRMT3, TYMS, DNMT3A, and HIF3A. Conclusions: FA supplementation influences the HCY level, as well as affects the cfDNA amount and the DNA methylation pattern. However, genetic factors may play a crucial role in mediating individual responses to folate intake, emphasizing the need for personalized approaches in managing hyperhomocysteinemia. Full article

Background/Objectives: Research on the safety and efficacy of high-dose folinic acid in Chinese children with autism spectrum disorder (ASD) is limited, and the impact of folate metabolism gene polymorphisms on its efficacy remains unclear. This trial aimed to evaluate the safety and efficacy of high-dose folinic acid intervention in Chinese children with ASD and explore the association between folate metabolism gene polymorphisms and efficacy. Methods: A 12-week randomized clinical trial was conducted, including 80 eligible children with ASD, randomly assigned to an intervention group (n = 50) or a control group (n = 30). The intervention group was administered folinic acid (2 mg/kg/day, max 50 mg/day) in two divided doses. Efficacy was measured using the Psycho-Educational Profile, Third Edition (PEP-3) at baseline and 12 weeks by two trained professionals blind to the group assignments. Methylenetetrahydrofolate reductase (MTHFR C677T, MTHFR A1298C), methionine synthase (MTR A2756G), and methionine synthase reductase (MTRR A66G) were genotyped by the gold standard methods in the intervention group. Results: 49 participants in the intervention group and 27 in the control group completed this trial. Both groups showed improvements from baseline to 12 weeks across most outcome measures. The intervention group demonstrated significantly greater improvements in social reciprocity compared to the control group. Children with MTHFR A1298C or MTRR A66G mutations demonstrated greater improvements in various developmental domains than wild type. Folinic acid may be more effective in certain genotype combinations, such as MTHFR C677T and A1298C. No significant adverse effects were observed during the intervention. Conclusions: High-dose folinic acid may be a promising intervention for children with ASD, and its efficacy is associated with folate metabolism gene polymorphisms. High-dose folinic acid intervention may promote better neurodevelopmental outcomes by alleviating folate metabolism abnormalities caused by single or combined mutations in folate metabolism genes. Full article

Introduction: Preeclampsia is a severe multifactorial complication of pregnancy. Studies found associations between folate metabolism genes’ polymorphisms and preeclampsia. However, investigations in this field are limited among Asian populations. Thus, the study’s aim was to evaluate the prevalence of methionine synthase (MTR), methionine synthase reductase (MTRR), and methylenetetrahydrofolate reductase (MTHFR) genes’ polymorphisms among ethnic Kazakh women with preeclampsia. Methods: This was a retrospective study involving 4246 patients’ data for the period of 2018–2022. Identification of MTR, MTRR, and MTHFR genes’ polymorphism was performed via PR-PCR. Peripheral blood samples were obtained for the analyses. In total, 4246 patients’ data of Kazakh ethnicity with preeclampsia at >20 weeks gestational age who had undergone an investigation to identify polymorphisms of the folate metabolism pathway genes for the period of 5 years were included in this study. Results: The most common and prevalent mutation was the MTRR A66G polymorphism: 24.5% of all tested patients with preeclampsia had the MTRR A66G polymorphism. It was highest among the 35–39 age group participants. The second most prevalent was the MTHFR C677T polymorphism: 9% of women with preeclampsia had the MTHFR C677T mutation. It was highest among women aged 30–34. There was a rare association of the MTR A2756G mutation with preeclampsia among the study participants. Conclusions: The identified levels of MTRR A66G and MTHFR C677T polymorphisms among the study participants suggest the importance of evaluating MTRR and MTHFR polymorphisms in women with preeclampsia. The role of the MTR A2756G polymorphism in the development of preeclampsia needs to be further investigated. Full article

Congenital heart disease is one of the most common congenital malformations and thus represents a considerable public health burden. Hence, the identification of individuals and families with an increased genetic predisposition to congenital heart disease (CHD) and its possible prevention is important. Even though CHD is associated with the lack of folate during early pregnancy, the genetic background of folate and methionine metabolism perturbations and their influence on CHD risk is not clear. While some genes, such as those coding for cytosolic enzymes of folate/methionine cycles, have been extensively studied, genetic studies of folate transporters (de)glutamation enzymes and mitochondrial enzymes of the folate cycle are lacking. Among genes coding for cytoplasmic enzymes of the folate cycle, MTHFR, MTHFD1, MTR, and MTRR have the strongest association with CHD, while among genes for enzymes of the methionine cycle BHMT and BHMT2 are the most prominent. Among mitochondrial folate cycle enzymes, MTHFD2 plays the most important role in CHD formation, while FPGS was identified as important in the group of (de)glutamation enzymes. Among transporters, the strongest association with CHD was demonstrated for SLC19A1. Full article

Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B vitamin supplements (methylfolate, pyridoxal-5′-phosphate, and methylcobalamin) on homocysteine and lipid levels, potentially guiding personalized CVD risk management. In a randomized, double-blind, placebo-controlled trial, 54 patients aged 40–75 with elevated homocysteine and moderate LDL-C levels were divided based on MTHFR, MTR, and MTRR genetic polymorphisms. Over six months, they received either a combination of methylfolate, P5P, and methylcobalamin, or a placebo. At the 6 months follow-up, the treatment group demonstrated a significant reduction in homocysteine levels by 30.0% (95% CI: −39.7% to −20.3%) and LDL-C by 7.5% (95% CI: −10.3% to −4.7%), compared to the placebo (p < 0.01 for all). In the subgroup analysis, Homozygous Minor Allele Carriers showed a more significant reduction in homocysteine levels (48.3%, 95% CI: −62.3% to −34.3%, p < 0.01) compared to mixed allele carriers (18.6%, 95% CI: −25.6% to −11.6%, p < 0.01), with a notable intergroup difference (29.7%, 95% CI: −50.7% to −8.7%, p < 0.01). LDL-C levels decreased by 11.8% in homozygous carriers (95% CI: −15.8% to −7.8%, p < 0.01) and 4.8% in mixed allele carriers (95% CI: −6.8% to −2.8%, p < 0.01), with a significant between-group difference (7.0%, 95% CI: −13.0% to −1.0%, p < 0.01). Methylfolate, P5P, and methylcobalamin supplementation tailored to genetic profiles effectively reduced homocysteine and LDL-C levels in patients with specific MTHFR, MTR, and MTRR polymorphisms, particularly with homozygous minor allele polymorphisms. Full article

The goal of this work was to determine the factors affecting the emergence of azithromycin-resistant Neisseria gonorrhoeae isolates in Russia, where azithromycin was never recommended for the treatment of gonococcal infections. Clinical N. gonorrhoeae isolates collected in 2018–2021 (428 isolates) were analyzed. No azithromycin-resistant isolates were found in 2018–2019, but in 2020–2021, a significant increase in the ratio of azithromycin-resistant isolates was observed: 16.8% and 9.3%, respectively. A hydrogel DNA microarray was developed for the analysis of resistance determinants: mutations in the genes encoding the mtrCDE efflux system and in all four copies of the 23S rRNA gene (position 2611). A majority of the azithromycin-resistant Russian isolates belonged to the NG-MAST G12302 genogroup, and the resistance was associated with the presence of a mosaic structure of the mtrR gene promoter region with the −35 delA deletion, an Ala86Thr mutation in the mtrR gene, and a mosaic structure of the mtrD gene. A comparative phylogenetic study of modern Russian and European N. gonorrhoeae populations allowed us to conclude that the emergence of azithromycin resistance in Russia in 2020 was the result of the appearance and spread of European N. gonorrhoeae strains belonging to the G12302 genogroup due to possible cross-border transfer. Full article

(1) Background. One of the causes of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is thrombus formation in situ followed by lysis, resulting in a morphologically normal angiogram but with an underlying prothrombotic state that is potentially predisposed to recurrence. Recent studies have shown that a subset of MINOCA patients may have thrombophilic conditions at screening. Objective: To compare the prothrombotic trend in MINOCA patients with that of subjects with MI and obstructive coronary arteries (MIOCA) by testing for known congenital thrombophilias and markers of coagulation activation. (2) Materials and methods. Screening included congenital thrombophilias (factor V Leiden; assessment of protein C, protein S, and antithrombin III) and eight genes. Of these, four genes represented the folate pathway enzymes: MTHFR 677 C>T (rs1801133), MTHFR 1298 A>C (rs1801131), MTR 2756 A>G (rs1805087), and MTRR 66 A>G (rs1801394). The other four genes represented the blood coagulation system: F13 (163 G>T) rs5985, F1 (−455 G>A) rs1800790, GP IIb–IIIa (1565 T>C) rs5918, and PAI-I (−675 5G>4G) rs1799889. Additionally, we examined the levels of homocysteine and lipoprotein (LP) (a). (3) Results. Our study included 269 patients: 114 MINOCA patients and 155 MIOCA patients with lesions of one coronary artery. The frequencies of polymorphisms in the genes of the blood coagulation system and the folate pathway did not differ between the groups. The following genes were associated with in-hospital mortality in the MINOCA group: MTHFR 1298 A>C rs1801131 (OR 8.5; 95% CI 1.67–43.1) and F1 (−455 G>A) rs1800790 (OR 5.8; 95% CI 1.1–27.8). In the MIOCA group, the following genes were associated with in-hospital mortality: MTHFR 1298 A>C rs1801131 (OR 9.1; 95% CI 2.8–28.9), F1 (−455 G>A) rs1800790 (OR 11.4; 95% CI 3.6–35.9), GP IIb–IIIa (1565 T>C) rs5918 (OR 10.5; 95% CI 3.5–30.8), and PAI-I (−675 5G>4G) rs1799889 (OR 12.9; 95% CI 4.2–39.7). We evaluated long-term outcomes (case fatality rate, recurrent MI, and stroke) over a period of 12 months in both groups. The variables associated with these outcomes were laboratory parameters, such as protein C deficiency, hyperhomocysteinemia, and a content of LP (a) > 30 mg/dL. However, we did not reveal the prognostic value of polymorphisms of the studied genes representing the blood coagulation system and the folate pathway. (4) Conclusion. We established no statistically significant differences between the MINOCA and MIOCA groups in the prevalence of congenital thrombophilias and the prevalence of folate pathway enzyme genes and blood coagulation system genes. The MTHFR 1298 A>C (rs1801131) and F1 (−455 G>A) rs1800790 genes were associated with in-hospital mortality in both groups. More significant prognostic factors in both groups during the one-year period were protein C deficiency, hyperhomocysteinemia, and LP (a) > 30 mg/dL. Full article