MTRR Gene Research Articles

Interrelationships among MTHFR gene polymorphisms, MTRR gene polymorphisms, and HBV gene BCP 1762/1764 mutations with disease progression in Chronic hepatitis B virus infection patients

Objective Chronic hepatitis B virus (HBV) infection is a major disease that seriously affects the health of patients. In this paper, the relationship among MTHFR gene polymorphism, MTRR gene polymorphism and 1762/1764 mutation in the BCP region of HBV gene with disease progression in chronic HBV patients was studied. Methods A total of 144 chronic HBV infection patients from January 2021 to June 2022 in the Third People’s Hospital of Zigong City, were included as the study subjects. These patients were divided into hepatitis B primary liver cancer patients group (PLC) in 51 cases, Non-primary liver cancer patients group (Non-PLC) in 93 cases, Non-PLC is also divided into chronic hepatitis B virus carriers (CHC) in 49 cases, hepatitis B Live cirrhosis(LC) in 44 cases. MTHFR (C677T), MTRR (A66G) and MTHFR (A1298C) genes polymorphisms were detected by PCR-dissolution curve. The level of HBV-DNA was quantified by real-time PCR, and the 1762/1764 mutation site in the BCP region of the HBV gene were detected by ARMS-PCR. Data were statistically analyzed using the SPSS statistical software. Results The proportion of HBV mutations in BCP region 1762/1764 in PLC group was 82.4%, which was higher than that in LC group (63.6%) and CHC group (51.0%), and the differences were statistically significant (p < 0.05). There were no significant differences in the distribution of MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms among CHC, LC and PLC (p > 0.05). The polymorphism distribution of MTHFR C677T, MTRR A66G and MTHFR A1298C genes in patients with chronic hepatitis B virus infection at different stages (CHC, LC and PLC) showed no gender or age differences between and within groups (p > 0.05). Among the patients with MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype, the proportion of HBV mutation in BCP region 1762/1764 in PLC group was higher than that in CHC group and LC group, and the differences were statistically significant (p < 0.05). Folate levels in the PLC group were lower than those in the non-PLC group (CHC and LC patients), and the difference was statistically significant compared with the CHC group (p < 0.05). In different MTHFR C677T and MTRR A66G genotypes, the serum GGT activity were statistically significant between mutant PLC and mutant Non-PLC (p < 0.05). Conclusion MTHFR C677T, MTRR A66G and MTHFR A1298C gene polymorphisms distribution have no gender and age differences in chronic hepatitis B virus infection patients. The mutation of HBV gene BCP region 1762/1764 may be associated with the occurrence and development of liver cancer in patients with chronic HBV infection. Single difference of MTHFR C677T, MTHFR A1298C and MTRR A66G gene polymorphisms may have little effect on the disease progression in patients with chronic HBV infection. MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype combined with HBV gene BCP region 1762/1764 mutation may be closely related to the occurrence and development of hepatitis B liver cancer.

Neisseria gonorrhoeae ST-1901 in Rio de Janeiro from 2006 to 2022: Phylogeny and antimicrobial resistance evolution of a well-succeeded pathogen

Neisseria gonorrhoeae is a global threat to public health due to the accumulation of antimicrobial resistance mechanisms. ST-1901 is an internationally important sequence type (ST) because of its high incidence and the usual occurrence of chromosomally determined resistance. In this study, we describe the evolution of the ST-1901 and its single locus variants in Rio de Janeiro from 2006 to 2022. We analyzed 82 N. gonorrhoeae isolates according to antimicrobial susceptibility profile, resistance mechanisms, molecular typing, and phylogenetics. Six different single locus variants were detected. Phylogenetic analysis identified five clades, which share similar characteristics. Resistance rates for penicillin and tetracycline decreased due to the lower occurrence of resistance plasmids, but intermediary resistance to penicillin rose. Resistance to ciprofloxacin remained high throughout all clades and the years of the study. Regarding resistance to azithromycin, alterations in mtrR promoter and gene, and 23S rRNA encoding gene rrl were detected, with a notable rise in the incidence of C2611T mutations in more recent years occurring in 4 out of 5 clades. In contrast, beta-lactam resistance associated penA 34 mosaic was found only in one persisting clade (Clade D), as well as unique G45D and A39T mutations in mtrR gene and its promoter (Nm-Like) were found in only Clade B. Taken together, these data suggest that ST-1901, a persistently circulating lineage of N. gonorrhoeae in Rio de Janeiro, has undergone changes over the years and may evolve to develop resistance to the current recommended dual therapy adopted in Brazil, ceftriaxone and azithromycin.

The role of single nucleotide variants of folate cycle genes of a mother with epilepsy in the occurrence of congenital malformations of the fetus

Aim - To study the frequency of single-nucleotide variants (ONV) rs1801133 and rs1801131 of the MTHFR gene; rs1801394 of the MTRR gene, rs1805087 of the MTR gene and rs1051266 of the SLC19A1 gene in women with epilepsy and to evaluate their associations with major congenital malformations (MCM) of the fetus. Material and methods. The study included 61 women with epilepsy who have children: 20 had different fetal MCM (main group), 41 patients had children born without MCM (comparison group). DNA was extracted from blood, and the genotyping of five ONV into four genes was analyzed by polymerase chain reaction. The frequencies of genotypes and alleles in the mothers of the main and the comparison group were determined, the differences were assessed using Pearson's chi-squared criterion (χ2) and Fisher's exact criterion. Results. There were no statistically significant differences in the frequencies of genotypes and alleles for all analyzed ONV between the main group and the comparison group. There were no statistically significant differences in the frequencies of genotypes and alleles of ONV genes of the folate cycle in mothers of children with malformations (n = 14) and without malformations (n = 22), taking valproic acid. A statistically significant relationship was revealed between the carrier of a certain haplogroup of the mother and the formation of fetal MCM. Conclusion. The MCM in a child is a multifactorial phenomenon in which genetic factors with a small effect size can play a significant role only in the case of certain unfavorable combinations.

Analysis of the contribution of polymorphisms of hemostasis system genes and folate cycle genes to the genetic presposition to the development of thrombosis in patients with Ph-negative myeloproliferative neoplasia in the Republic of Uzbekistan

Thrombotic complications often complicate the course of the underlying disease in patients with chronic myeloproliferative neoplasia. However, a thromboembolic condition is not observed in all patients.The aim of the study was to assess the carriage frequency of polymorphic genes of the blood coagulation system and folate metabolism genes and the contribution of genetic variants to the development of thrombosis in patients with chronic Ph-negative myeloproliferative neoplasia (CMPN).Materials and methods. Molecular genetic testing for the presence of genetic variants with an assessment of their frequency of occurrence and allelic load was carried out in 142 patients with CMPN. We studied polymorphisms of the folate cycle genes – A2756G (Asp919Gly) of the MTR gene, C677T (Ala22Val) of the MTHFR gene, A66G (ILe22Met) of the MTRR gene (rs1801394), as well as mutations of the genes of blood coagulation factors – G(455)A of the FGB gene, G20210A of the F2 gene, G10976A (Arg353Gln) of the F7 gene, G1691A (Arg506Gln) of the F5 gene. The study was carried out using real-time polymerase chain reaction (PCR); The biological material for the test was whole blood.Results and discussion. The study showed that only 6 out of 50 (12%) patients with thrombotic complications had no changes in the genes studied, while 88% of patients had one or another genotypic variant, which may indicate a high probability of involvement of a hereditary genetic factor in the development of hypercoagulability and thrombotic complications in patients with chronic MPN.Conclusions. A comprehensive study of the role, interaction and operating conditions of genes that control blood coagulation processes in patients with Ph-negative chronic MPN will make it possible to understand the causes of hemostatic system disorders and develop effective measures to prevent thrombotic complications in this category of patients.

Impact of mutations in the mtrR, rpdlVD and rrl genes on azithromycin resistance in Neisseria gonorrhoeae.

Bacterial sexually transmitted infections (STIs) pose a major public health problem. The emergence of antibiotic-resistant strains of Neisseria gonorrhoeae represents a serious threat to successful treatment and epidemiological control. The first extensively drug-resistant (XDR) strains (ceftriaxone-resistant and high-level azithromycin-resistant [HLR AZY]) have been reported. To identify molecular mechanisms implicated in azithromycin resistance in strains isolated from patients over a three-year period in a university hospital in Switzerland. From January 2020 to December 2022, 34 isolates (one per patient) were recovered from samples analyzed at the University Hospital of Lausanne. Eight genes involved in azithromycin resistance were sequenced: mtrR repressor (mtrCDE operon repressor) and his promotor mtrR-pr, rplD gene (L4 ribosomal protein), rplV gene (L22 ribosomal protein) and the four alleles of the rrl gene (23S rRNA). With a cutoff value of 1 mg/L, 15 isolates were considered as being resistant to azithromycin, whereas the remaining 19 were susceptible. The C2597T mutation in 3 or 4 of the rrl allele confer a medium-level resistance to azithromycin (MIC = 16 mg/L, N = 2). The following mutations were significantly associated with MIC values ≥1 mg/L: the three mutations V125A, A147G, R157Q in the rplD gene (N = 10) and a substitution A->C in the mtrR promotor (N = 9). Specific mutations in the mtrR repressor and its promotor were observed in both susceptible and resistant isolates. Resistance to azithromycin was explained by the presence of mutations in many different copies of 23S RNA ribosomal genes and their regulatory genes. Other mutations, previously reported to be associated with azithromycin resistance, were documented in both susceptible and resistant isolates, suggesting they play little role, if any, in azithromycin resistance.

Association of MTHFR (C677T, A1298C) and MTRR A66G polymorphisms with fatty acids profile and risk of neural tube defects.

This study aims to determine if 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase reductase (MTRR A66G) gene polymorphisms were associated with fatty acid (FA) levels in mothers of fetuses with neural tube defects (NTDs) and whether these associations were modified by environmental factors. Plasma FA composition was assessed using capillary gas chromatography. Concentrations of studied FA were compared between 42 mothers of NTDs fetuses and 30 controls as a function of each polymorphism by the Kruskal-Wallis nonparametric test. In MTHFR gene C677T polymorphism, cases with (CT + TT) genotype had lower monounsaturated FAs (MUFA) and omega-3 polyunsaturated FA (n-3 PUFA) levels, but higher omega-6 polyunsaturated FAs (n-6 PUFA) and omega-6 polyunsaturated FAs: omega-3 polyunsaturated FAs (n-6:n-3) ratio levels. In MTRR gene A66G polymorphism, cases with (AG + GG) genotype had lower MUFA levels, but higher PUFA and n-6 PUFA levels. Controls with (AG + GG) genotype had lower n-6 PUFA levels. In MTHFR gene C677T polymorphism, cases with smoking spouses and (CT + TT) genotype had lower MUFA and n-3 PUFA levels, but higher PUFA, n-6 PUFA, and n-6:n-3 ratio levels. Cases with (CT + TT) genotype and who used sauna during pregnancy had lower n-3 PUFA levels. In MTRR gene A66G polymorphism, cases with (AG + GG) genotype and who used sauna during pregnancy had higher PUFA and n-6 PUFA levels. Further research is required to clarify the association of FA metabolism and (MTHFR, MTRR) polymorphisms with NTDs.

Polymorphic substitutions in folate cycle genes as predictors of hyperhomocysteinemia in children

Introduction. Mutant alleles of genes of folate cycle enzymes can lead to the significant deterioration of its function and varying severity of pathology. Several defects in these genes lead to severe hyperhomocysteinemia, the most common form of which is a deficiency of cystathionine beta-synthase B. &#x0D; Aim: to establish polymorphic substitutions in the genes of folate cycle enzymes that contribute to the formation of hyperhomocysteinemia in children.&#x0D; Materials and methods. Two hundred seventy one children aged of 13–18 years were examined. The analysis of genetic polymorphisms of the folate cycle was carried out using a molecular genetic method. Quantitative determination of the blood homocysteine and folic acid level was performed by chemiluminescent immunoassay on microparticles. Statistical data processing was carried out using Statistica 6.1 application programs (StatSoft Inc., USA). &#x0D; Results. The frequency of the T allele of the MTHFR 677 gene was revealed to be higher in adolescents of the main group compared with the control (p = 0.043). The frequency of the homozygous genotype 66 AA of the MTRR gene in children of the comparison group was significantly higher (p = 0.049), however, the heterozygous genotype 66 AG of the MTRR gene was significantly more often detected in adolescents of the main group (p = 0.008). The average concentrations of homocysteine in children of the main group were 11.6 mmol/L, in adolescents of the control group 9.3 mmol/L (p = 0.021). Hyperhomocysteinemia in children of the main group was detected in 217 (80.1%) adolescents, and in 57 (49.6%) children of the control group (p &lt; 0.001). The baseline serum folate level was determined in the children of the main group. The average amount of vitamin B9 in the blood of children of the main group was 3.7 ng/ml, and in 145 (53.5%) children this indicator was significantly reduced.&#x0D; Conclusion. Low levels of folic acid contribute to an increase in homocysteine in blood plasma. Taking vitamin B9 and vitamin folate complexes significantly reduces the level of homocysteine in blood plasma (p &lt; 0.001).

MTRR gene rs1801394 polymorphism is associated with neonatal birth weight in pregnant women with fetal growth retardation

Aim: to assess associations between folate cycle gene polymorphism and neonatal birth weight in pregnant women with fetal growth retardation (FGR) and related functional effects in population of the Central Black Earth Region.Materials and Methods. 98 cases of women with FGR were enrolled to a retrospective molecular and genetic screening to assess prevalence 5 SNPs (single nucleotide polymorphisms) in genes involved in folic acid cycle and methionine metabolism (rs699517 TYMS, rs2790 TYMS, rs1979277 SHMT1, rs1805087 MTR, rs1801394 MTRR).Results. It was found out that allele A of the rs1801394 MTRR was associated with a lower neonatal birth weight (recessive model: β = –0.34 ± 0.13; p = 0.009). This polymorphic locus exerts crucial functional effects by determining the amino acid substitution in methionine synthase reductase (Ile22Met) localized in the region of modified histones, which mark enhancers and promoters in ectoderm, endoderm and mesoderm cell cultures, primary osteoblast cells, brain, fat nuclei, skeletal muscles, etc. In addition, rs1801394 MTRR is found DNA sites (motifs) responsible for sensitivity to transcription factors STAT and TBX5 being also related to MTRR gene mRNA expression level in subcutaneous and visceral adipose tissue, thyroid gland, fibroblast cell culture as well as various brain regions.Conclusion. Thus, the allele A of the rs1801394 polymorphism in MTRR gene is a risk factor for a lower neonatal birth weight.

Genetic Association between the Risk of Dental Caries and MTR Gene Polymorphism in Chinese Children.

Early childhood caries (ECC) is common in children. Little is known about the genetic association of the methionine synthesis reductase (MTRR) gene rs1801394 and methionine synthetase (MTR) gene rs1805087 polymorphisms with ECC, which was examined in the Chinese Han population. Genotyping was performed using the buccal mucosa from 150 normal and 150 ECC children. For genotype and allele distribution comparison, Chi-square test and multiple logistic regression analysis were performed. The odd ratio (OR) and 95% confidence interval (CI) were calculated. MTR gene rs1805087 AG genotype distribution in the ECC group was clearly different from the control group (P = 0.029), and the ECC risk in cases with AG genotype was 0.525 times lower than those carrying AA genotype (95% CI = 0.292-0.942). Logistic regression analysis after adjustment for other clinical indicators determined that the MTR gene rs1805087 AG genotype was still strongly associated with susceptibility to ECC (OR = 0.499, 95% CI = 0.273-0.913, P = 0.024). Significant association was also seen for sugary food intakes (OR = 1.965, 95% CI = 1.162-3.321, P = 0.012), tooth brushing (OR = 0.569, 95% CI = 0.356-0.924, P = 0.023) and sex (OR = 0.562, 95% CI = 0.349-0.907, P = 0.018) with ECC risk. No notable genetic association was found between MTRR gene rs1801394 polymorphism and ECC risk. MTR gene rs1805087 polymorphism may aggrandize the susceptibility to ECC, and AA genotype appeared to be a dangerous element for the development of ECC.

Methionine sources at different dietary levels alters the growth and expression of genes related to homocysteine remethylation in the jejunum of broilers.

Sulfur amino acids are essential for the proper development of broilers and are required throughout the bird's life to perform important physiological functions. Studies that seek to understand the actions of sulfur amino acids in the body of birds are essential. The present study evaluated the influence of sulfur amino acid supplementation using DL-Methionine (DL-Met) and DL-Methionine hydroxy analogue (DL-HMTBA), on the performance and expression of genes related to methionine metabolism, in the jejunum of broilers. Four hundred and fifty male broilers (Cobb-700 slow feathering) were distributed in a completely randomized design, in a factorial scheme (2x3), with two sources of methionine (DL-Met and DL-HMTBA) and three levels of methionine (deficiency, requirement and excess). The mRNA expression of the MAT1, MTR, BHMT, MTRR, CBG and GSS genes, and performance data such as feed intake, weight gain, and feed conversion were evaluated. DL-HMTBA increased the expression of BHMT (p = 0.0072) and MTRR (p = 0.0003) in the jejunum of the birds. Methionine deficiency increased the expression of BHMT (p = 0.0805) and MTRR (p = 0.0018). Higher expression of GSS was observed in birds that were supplemented with DL-HMTBA (p = 0.0672). Analyzing our results, it is preferable to supplement sulfur amino acids with DL-Met at the requirement level. Birds fed with DL-HMTBA showed worse weight gain (p = 0.0117) and higher feed conversion (p = 0.0170); methionine deficiency resulted in higher feed intake (p = 0.0214), lower weight gain (p<0.0001) and consequently higher feed conversion (p<0.0001). Based on the information found in this work, it is recommended to supplement sulfur amino acids with DL-Met at the level of compliance with the requirement.

Antimicrobial susceptibility profile of Neisseria gonorrhoeae from patients attending a medical laboratory, Institut Pasteur de Madagascar between 2014 and 2020: phenotypical and genomic characterisation in a subset of Neisseria gonorrhoeae isolates

ObjectivesAntimicrobial-resistant Neisseria gonorrhoeae (NG) is a concern. Little is known about antimicrobial susceptibility profiles and associated genetic resistance mechanisms of NG in Madagascar. We report susceptibility data of NG isolates...

Allelic variants of folate metabolism genes among students in Arctic Russia

AIM: To assess the prevalence of allelic variants of folate metabolism genes in Russian and Indian students living in the Arctic region of Russia.&#x0D; METHODS: A cross-sectional study was performed on a sample of ethnic Indians, students at the Faculty of General Practitioner of the Northern State Medical University, living in Arkhangelsk and ethnic Russians who were born in Arkhangelsk region. The study included 117 ethnic Indians and 195 Russian participants. A survey of participants and a molecular genetic study of the nucleotide sequence in the genes involved in the exchange of folate by real-time PCR were carried out. A group of ethnic Indians was compared with Russians according to 4 variants of the nucleotide sequence in the genes involved in folate metabolism.&#x0D; RESULTS: Statistically significant differences were observed in the frequency distribution of the T allele of the MTHFR gene polymorphism (rs1801133) (p=0.001). Among Russians, the occurrence of the T allele was found to be 26.3%, whereas among Indians, it was only 7.7%. At the same time, no statistically significant differences were found in the distribution of other polymorphic variants of the folate cycle genes between the groups. The mutant allele G of the MTRR gene polymorphism (rs1801394) was the most frequently occurring polymorphism among the participants.&#x0D; CONCLUSION: Greater prevalence of the unfavorable allele T of the MTHFR gene (rs1801133) compared to the group of ethnic Indians may suggest an elevated susceptibility to folate metabolism disorders in the Russian population

The role of hereditary thrombophilia in the development of venous thrombosis in combat trauma

Introduction. Combat trauma is one of the factors causing hemostasis disorders in the wounded. Currently, there is insufficient information about the significance of hereditary thrombophilia in the development of venous thromboembolic complications in the wounded.Aim. To study the effect of polymorphism of genes of components of the hemostasis system on the development of venous thrombosis in wounded with combat trauma.Materials and methods. The prospective study included men (n = 81) of young age (the average age was 36.0 ± 8.5 years) who received a combat wound and were treated at the Military Medical Academy named after S.M. Kirov. The subjects were divided into 2 groups: the main group included 40 victims (49.4%) who were diagnosed with venous thrombosis during treatment, the control group included 41 patients without signs of thrombosis (50.6%). The study of allelic polymorphism of genes associated with the formation of blood clots was carried out using a real-time polymerase chain reaction based on the study of human DNA in peripheral blood material.Results. Comparative analysis revealed no statistically significant differences in the frequency of occurrence of the studied genetic variants between the study group and the control group. When assessing the prevalence of polymorphism of the MTHFR and MTRR genes, it was found that the combination of the genotypes “MTHFR 677 CT” and “MTRR 66 GG” is associated with an 8.5-fold increase in the risk of developing VTEO [OR = 8.5; p = 0.029].Conclusion. Analysis of the test results showed that no relationship was found between individual genetic variants and the risk of developing venous thrombosis in the studied group of wounded despite the high prevalence (prothrombogenic alleles of various genes were detected in 79 servicemen (97.5%)). At the same time, the combination of MTHFR 677 CT and MTRR 66 GG genotypes in that patient population was shown to be associated with a significant increase in the risk of thrombosis.

THE CONTENT OF ENDOTHELIN-1 IN THE BLOOD PLASMA OF PATIENTS WITH DIABETIC RETINOPATHY ON THE BACKGROUND OF TYPE 2 DIABETES DEPENDING ON THE POLYMORPHIC VARIANTS OF THE MTHFR, MTRR AND MTR GENES

Backround. The vascular and extravascular microcirculation of the eye is a rich source of endothelin-1 (ET-1), which can contribute to abnormal retinal hemodynamics in diabetic retinopathy. In patients with type 2 diabetes mellitus (T2DM), an increase in the level of circulating ET-1 was found, and a positive correlation between its levels in the blood was found and degree of microangiopathy. Strengthens the development of endothelial dysfunction and microvascular complications, a high level of homocysteine, which occurs due to a genetically determined deficiency of enzymes of the folate cycle, determines in the body what, because homocysteine ​​causes a violation of the structure of endothelial cells.&#x0D; Aim: to study the ET-1 content in the blood plasma of patients with diabetic retinopathy against the background of type 2 diabetes, depending on the polymorphic variants of the MTHFR, MTRR and MTR genes, as an important pathogenetic pathway for the development of endothelial dysfunction.&#x0D; Materials and methods. The study included 83 patients (83 eyes) with T2DM, in whom non-proliferative and proliferative DR were found according to the results of an ophthalmological examination using the ETDRS scale. The control group (CG) included 35 people without diabetes, who were matched with patients by gender, age, and body mass index. Gene polymorphism was determined using real-time PCR on the automatic amplifier Gene Amp® PCR System 7500, the content of ET-1 was determined in blood plasma by the ELISA method.&#x0D; Conclusion. The SS genotype of the rs1801133 gene, the GG genotype of the rs1805087 gene, the AS polymorphism, and the SS genotype of the rs1801131 gene can be considered potential risk factors for the development of DR on the background of type 2 diabetes.&#x0D; The SS genotype of the rs1801133 gene was accompanied by a maximum 14-fold increase in ET-1 in patients with DR. The minor GG genotype of the rs1805087 gene was found only in patients with DR, and was characterized by the maximum content of ET-1. In the carriers of AS polymorphism of the rs1801131 gene, an 8-fold increase in ET-1 was found during the development of DR.&#x0D; The minor GG genotype of the rs1805087 gene was found only in patients with DR, and was characterized by the maximum content of ET-1. In the carriers of AS polymorphism of the rs1801131 gene, an 8-fold increase in ET-1 was found during the development of DR. The minor SS genotype of this gene was twice as common in patients, and the ET-1 content increased 5 times with the development of DR.&#x0D; The presence of ST polymorphism of the rs1801133 gene and the AA genotype of rs1801131 are probably factors that prevent the development of DR. The ST gene rs1801133 polymorphism was accompanied by the lowest ET-1 content. The AA genotype of the rs1801131 gene was 1.3 times less frequent, the ET-1 content in these individuals was the lowest and practically did not change during the development of DR.

Association of methionine synthase reductase (MTRR A66G) polymorphism with susceptibility to acute lymphoblastic leukemia

Background and Objectives. The enzyme methionine synthase reductase is involved in cellular methylation reactions, DNA synthesis, and epigenetic processes. It is encoded by the MTRR gene, which garnered a lot of attention in current medical genetics research. This study was conducted to study the association between MTRR (A66G) polymorphism and the risk of developing acute lymphoblastic leukemia among Sudanese patients. Materials and Methods. This is a case-control study in which 150 patients with acute lymphoblastic leukemia (ALL) and 150 healthy participants as a control group were enrolled. DNA was extracted and analyzed for the MTRR (A66G) polymorphism using the real-time polymerase chain reaction. Results. Based on flow cytometry results, B-ALL was more common (79%) than T-ALL (21%). The comparison of hematological parameters in acute lymphoblastic leukemia subtypes showed a statistically significant high mean total white blood count (P=0.000) and mean blast percentage (P=0.050) in patients with T-ALL. The molecular analysis showed that the incidence of the MTRR homozygous genotypes AA and GG were higher in the patients (44% and 9.3%, respectively) compared to the control group (40% and 6.7%, respectively). In comparison, the heterozygous genotype AG was lower in the patients (46.7%) than in the control group (53.3%). However, the association between the polymorphism and acute lymphoblastic leukemia risk was not statistically significant (OR: 1.179, 95% CI 0.7459-1.865, P=0.445). Conclusions. This study concluded that MTRR A66G polymorphism was not associated with the risk of acute lymphoblastic leukemia among the Sudanese population.

ИЗУЧЕНИЕ ВЛИЯНИЯ НАСЛЕДСТВЕННЫХ ТРОМБОФИЛИЙ В РАЗВИТИИ ВЕНОЗНЫХ ТРОМБОЗОВ ПРИ БОЕВОЙ ТРАВМЕ

Introduction. Combat trauma is one of the factors that cause impaired hemostasis in the wounded. Currently, there is not enough information about the significance of hereditary thrombophilia in the development of venous thromboembolic complications in the wounded. Target. Study of the effect of polymorphism of the genes of the components of the hemostasis system on the development of venous thrombosis in the wounded with a combat injury. Materials and methods. The prospective study included young men (n=81) (mean age 36.0 ± 8.5 years) who received a combat wound and were treated at the Military Medical Academy. CM. Kirov. The subjects were divided into 2 groups: the main group included 40 patients (49.4%) who were diagnosed with venous thrombosis during treatment, the control group included 41 patients without signs of thrombosis (50.6%). The study of allelic polymorphism of genes associated with the process of thrombus formation was carried out using a real-time polymerase chain reaction based on the study of human DNA in peripheral blood material. Results. In a comparative analysis, no statistically significant differences were found in the frequency of occurrence of the studied genetic variants between the study group and the control group. When assessing the prevalence of polymorphisms in the MTHFR and MTRR genes, it was found that the combination of the MTHFR 677 CT and MTRR 66 GG genotypes is associated with an 8.5-fold increase in the risk of developing venous thromboembolic complications [OR=8.5; p=0.029]. Conclusion. The analysis of the obtained results showed that, despite the high prevalence (the presence of prothrombogenic alleles of various genes was detected in 79 military personnel (97.5%)), it was not possible to establish a relationship between individual genetic variants and the risk of developing venous thrombosis in the studied group of wounded. At the same time, it has been shown that the combination of the MTHFR 677 CT and MTRR 66 GG genotypes is associated with a significant increase in the risk of thrombosis.

Antimicrobial susceptibilities and genomic epidemiology of Neisseria gonorrhoeae in Stockholm, Sweden.

The aim of this study was to investigate the genomic epidemiology and antimicrobial susceptibilities of N. gonorrhoeae isolates in Stockholm, Sweden. In total, 6723 isolates detected in Stockholm, Sweden, from January 2016 to September 2022, were examined for antimicrobial susceptibilities by using E-test. Whole-genome sequencing (WGS) was applied to isolates in sentinel surveillance and isolates resistant to extended-spectrum cephalosporins (ESCs) or high-level azithromycin (HLAzi-R, MIC ≥ 256 mg/L). As sentinel surveillance, consecutive clinical isolates (n = 396) detected every 4th week from January 2021 to September 2022 were enrolled in the study. Of the 6723 isolates investigated, 33 isolates (< 1%) were found to be resistant to cefixime, one of which was co-resistant to ceftriaxone and ciprofloxacin and was detected in September 2022. Ten isolates presented a high level of azithromycin resistance. Resistant rates to ciprofloxacin varied from 32 in 2017 to 68-69% in 2021-2022. Elevated MIC50 and MIC90 of azithromycin were observed over the years. No resistance to spectinomycin was identified. The most frequently occurring MLST in the sentinel surveillance was ST9362 (23%), followed by ST11706 (9%), ST7359 (8%), ST10314 (7%), and ST11422 (6%). The ceftriaxone-resistant isolate belonged to ST8130 and the novel NG-STAR ST4859. Genomic resistance traits found in this strain included mutations in genes mtrR (A39T), parC (S87N), and gyrA (S91F and D95A), as well as the presence of blaTEM-135 and tetM genes. A predominance of ST9362 was observed in Stockholm. The high number of azithromycin and ciprofloxacin-resistant isolates and the emergence of a strain with a novel NG-STAR are of great concern.

Association of maternal methionine synthase reductase gene polymorphisms with the risk of congenital heart disease in offspring: a hospital-based case-control study

Background Evidence suggests that periconceptional folic acid supplementation may prevent congenital heart disease (CHD). Methionine synthase reductase (MTRR) is one of the key regulatory enzymes in the folate metabolic pathway. This study aimed to comprehensively evaluate the association of single nucleotide polymorphisms (SNPs) in the maternal MTRR gene with CHD risk in offspring. Methods A hospital-based case-control study involving 740 mothers of CHD cases and 683 health controls was conducted. Results The study showed that maternal MTRR gene polymorphisms at rs1532268 (C/T vs. C/C: aOR = 1.524; T/T vs. C/C: aOR = 3.178), rs1802059 (G/A vs. G/G: aOR = 1.410; A/A vs. G/G: aOR = 3.953), rs2287779 (G/A vs. G/G: aOR = 0.540), rs16879334 (C/G vs. C/C: aOR = 0.454), and rs2303080 (T/A vs. T/T: aOR = 0.546) were associated with the risk of CHD. And seven haplotypes were observed to be associated with the risk of CHD, T-G-A haplotype (OR = 1.298), C-A-C-C (OR = 4.824) and A-G haplotype (OR = 1.751) were associated with increased risk of CHD in offspring; A-A-A (OR = 0.773), T-A-A (OR = 0.557), G-A-C-C (OR = 0.598) and G-C (OR = 0.740) were associated with decreased risk of CHD in offspring. Conclusions Maternal MTRR gene polymorphisms were associated with CHD in offspring, and its haplotypes have affected the occurrence of CHD. Furthermore, given the complexity and heterogeneity of CHD, the mechanisms by which these factors influence offspring cardiac development remain unknown, and studies in larger samples in an ethnically diverse population are needed.

Association analysis of MTHFR (rs1801133 and rs1801131) and MTRR (rs1801394) gene polymorphisms towards the development of hypertension in the Bai population from Yunnan, China

ABSTRACT Objective Hypertension is one of the leading causes of human death and disability. MTHFR and MTRR regulate folate metabolism and are closely linked to hypertension, although the relationship is inconsistent among different ethnic groups. The present study aims to investigate the effects of MTHFR C677T (rs1801133), MTHFR A1298C (rs1801131), and MTRR A66G (rs1801394) polymorphisms on hypertension susceptibility in the Bai nationality of the Yunnan Province, China. Methods This case–control study included 373 hypertensive patients and 240 healthy controls from the Chinese Bai population. The genotyping of MTHFR and MTRR gene polymorphisms was carried out by using the KASP method. The effects of genetic variations of MTHFR and MTRR genes on hypertension risk were evaluated with odds ratios (OR) and 95% confidence intervals (95% CI). Results The present study revealed that the CT and TT genotypes and T allele of MTHFR C677T locus were considerably associated with an increased risk of hypertension. In addition, MTHFR A1298C locus CC genotype could significantly increase the hypertension risk. The T-A and C–C haplotypes of MTHFR C677T and MTHFR A1298C could increase the risk of hypertension. Further stratified analysis by risk rank of folate metabolism indicated that people with poor utilization of folic acid were more prone to develop hypertension. In the hypertension group, the MTHFR C677T polymorphism was significantly associated with fasting blood glucose, fructosamine, apolipoprotein A1, homocysteine, superoxide dismutase, and malondialdehyde levels. Conclusion Our study suggested that genetic variations of MTHFR C677T and MTHFR A1298C were significantly associated with susceptibility to hypertension in the Bai population from Yunnan, China.

Emergence of Azithromycin-Resistant Neisseria gonorrhoeae Isolates Belonging to the NG-MAST Genogroup 12302 in Russia

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.