The genetic variant rs55986091 HLA-DQB1 is associated with a protective effect against cervical cancer.

Introduction: Cervical cancer (CC) is a prevalent malignancy affecting women globally. The primary causative factor of CC is the high-risk oncogenic human papillomavirus (HR-HPV). However, it is noteworthy that not all women infected with HR-HPV develop cancer, indicating the potential involvement of genetic predisposition in the development of CC. This study aims to identify genetic risks and their distribution in groups of women with different epidemiological features of HR-HPV. Materials and methods: A comparison was conducted among four groups of women, comprising 218 HPV-negative women, 120 HPV-positive women, 191 women diagnosed with cervical intraepithelial neoplasia (CIN) grade 2 or 3, and 124 women diagnosed with CC. The analysis focused on four single nucleotide polymorphisms (SNPs): rs55986091 in HLA-DQB1, rs138446575 in TTC34, rs1048943 in CYP1A1, and rs2910164 in miRNA-146a. Results: The rs55986091-A allele exhibited a protective effect within the "CC" group when compared to the "HPV-Negative" group (OR = 0.4, 95% CI= 0.25-0.65) using a log-additive model. Additionally, similar protective effects were observed in the "CIN 2/3" group compared to the "HPV-Negative" group (OR = 0.47, 95% CI = 0.28-0.79). Conclusion: The data obtained emphasize the importance of developing PCR-based diagnostic kits for the identification of SNP alleles, particularly for rs55986091, among HR-HPV-positive women within the Russian population.

Association of Toll-Like Receptor Gene Polymorphisms with Tuberculosis in HIV-Positive Participants.

Genetic factors in the HIV-background may play a significant role in the susceptibility to secondary diseases, like tuberculosis, which is the leading cause in mortality of HIV-positive people. Toll-like receptors (TLRs) are considered to be receptors for adaptive immunity, and polymorphisms in TLR genes can influence the activity of the immune response to infection. We conducted a case-control study of the association of TLR gene polymorphisms with the risk of tuberculosis coinfection in a multi-country sample of HIV-positive participants. Our study revealed certain associations between TLR4 and TLR6 polymorphisms and HIV-tuberculosis coinfection. We also found that the analyzed TLR1 and TLR4 polymorphisms were linked with the decline in CD4+ cell count, which is a predictor of disease progression in HIV-infected individuals. Our findings confirm that TLR gene polymorphisms are factors that may contribute to development of HIV-tuberculosis coinfection. However, the essence of the observed associations remains unclear, since it can also include both environmental factors and epigenetic mechanisms of gene expression regulation.

Development and Application of Real-Time PCR-Based Screening for Identification of Omicron SARS-CoV-2 Variant Sublineages.

The Omicron strain is currently the main dominant variant of SARS-CoV-2, with a large number of sublineages. In this article, we present our experience in tracing it in Russia using molecular diagnostic methods. For this purpose, different approaches were used; for example, we developed multiprimer panels for RT-PCR and Sanger and NGS sequencing methods. For the centralized collection and analysis of samples, the VGARus database was developed, which currently includes more than 300,000 viral sequences.

SARS-CoV-2 Variants Monitoring Using Real-Time PCR.

According to the temporary recommendations of the 2021 World Health Organization (WHO), in addition to whole-genome sequencing, laboratories in various countries can also screen for known mutations utilizing targeted RT-PCR-based mutation detection assays. The aim of this work was to generate a laboratory technique to differentiate the main circulating SARS-CoV-2 variants in 2021-2022, when a sharp increase in morbidity was observed with the appearance of the Omicron variant. Real-time PCR methodology is available for use in the majority of scientific and diagnostic institutions in Russia, which makes it possible to increase the coverage of monitoring of variants in the territories of all 85 regions in order to accumulate information for the Central Services and make epidemiological decisions. With the methodology developed by the Central Research Institute of Epidemiology of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing (FSSCRP Human Wellbeing) (CRIE), more than 6000 biological samples have been typed, and 7% of samples with the Delta variant and 92% of samples with the Omicron variant have been identified as of 25 August 2022. Reagents for 140,000 definitions have been supplied to regional organizations.

TLRs Gene Polymorphisms Associated with Pneumonia before and during COVID-19 Pandemic.

BACKGROUND: The progression of infectious diseases depends on the characteristics of a patient's innate immunity, and the efficiency of an immune system depends on the patient's genetic factors, including SNPs in the TLR genes. In this pilot study, we determined the frequency of alleles in these SNPs in a subset of patients with pneumonia. METHODS: This study assessed six SNPs from TLR genes: rs5743551 (TLR1), rs5743708, rs3804100 (TLR2), rs4986790 (TLR4), rs5743810 (TLR6), and rs3764880 (TLR8). Three groups of patients participated in this study: patients with pneumonia in 2019 (76 samples), patients with pneumonia caused by SARS-CoV-2 in 2021 (85 samples), and the control group (99 samples). RESULTS: The allele and genotype frequencies obtained for each group were examined using four genetic models. Significant results were obtained when comparing the samples obtained from individuals with pneumonia before the spread of SARS-CoV-2 and from the controls for rs5743551 (TLR1) and rs3764880 (TLR8). Additionally, the comparison of COVID-19-related pneumonia cases and the control group revealed a significant result for rs3804100-G (TLR2). CONCLUSIONS: Determining SNP allele frequencies and searching for their associations with the course of pneumonia are important for personalized patient management. However, our results need to be comprehensively assessed in consideration of other clinical parameters.

Prevention and control of meningococcal disease: Updates from the Global Meningococcal Initiative in Eastern Europe.

The Global Meningococcal Initiative (GMI) aims to prevent invasive meningococcal disease (IMD) worldwide through education, research and cooperation. In March 2019, a GMI meeting was held with a multidisciplinary group of experts and representatives from countries within Eastern Europe. Across the countries represented, IMD surveillance is largely in place, with incidence declining in recent decades and now generally at <1 case per 100,000 persons per year. Predominating serogroups are B and C, followed by A, and cases attributable to serogroups W, X and Y are emerging. Available vaccines differ between countries, are generally not included in immunization programs and provided to high-risk groups only. Available vaccines include both conjugate and polysaccharide vaccines; however, current data and GMI recommendations advocate the use of conjugate vaccines, where possible, due to the ability to interrupt the acquisition of carriage. Ongoing carriage studies are expected to inform vaccine effectiveness and immunization schedules. Additionally, IMD prevention and control should be guided by monitoring outbreak progression and the emergence and international spread of strains and antibiotic resistance through use of genomic analyses and implementation of World Health Organization initiatives. Protection of high-risk groups (such as those with complement deficiencies, laboratory workers, migrants and refugees) is recommended.

Application of the genetic risk model for the analysis of predisposition to nonlacunar ischemic stroke.

Aim: The purpose of our study was to analyze the predictive ability of the multiplicative model of genetic risk of nonlacunar ischemic stroke (IS) for independent samples from Russia. Patients & methods: A total of 181 patients and 360 healthy controls were included in this study. The discriminative accuracy of model was evaluated by the area under the receiver operating characteristic curve (AUC). Results: Classification model based on 15 single-nucleotide polymorphisms (SNPs), which are associated with a cardioembolic subtype of IS, had an AUC of 0.62 in patients with corresponding subtypes and an AUC of 0.58 for all patients. Conclusion: Risk calculation approach based on IS-associated SNPs had satisfactory performance in predicting the predisposition to the disease.

The Global Meningococcal Initiative meeting on prevention of meningococcal disease worldwide: Epidemiology, surveillance, hypervirulent strains, antibiotic resistance and high-risk populations.

INTRODUCTION: The 2018 Global Meningococcal Initiative (GMI) meeting focused on evolving invasive meningococcal disease (IMD) epidemiology, surveillance, and protection strategies worldwide, with emphasis on emerging antibiotic resistance and protection of high-risk populations. The GMI is comprised of a multidisciplinary group of scientists and clinicians representing institutions from several continents. AREAS COVERED: Given that the incidence and prevalence of IMD continually varies both geographically and temporally, and surveillance systems differ worldwide, the true burden of IMD remains unknown. Genomic alterations may increase the epidemic potential of meningococcal strains. Vaccination and (to a lesser extent) antimicrobial prophylaxis are the mainstays of IMD prevention. Experiences from across the globe advocate the use of conjugate vaccines, with promising evidence growing for protein vaccines. Multivalent vaccines can broaden protection against IMD. Application of protection strategies to high-risk groups, including individuals with asplenia, complement deficiencies and human immunodeficiency virus, laboratory workers, persons receiving eculizumab, and men who have sex with men, as well as attendees at mass gatherings, may prevent outbreaks. There was, however, evidence that reduced susceptibility to antibiotics was increasing worldwide. EXPERT COMMENTARY: The current GMI global recommendations were reinforced, with several other global initiatives underway to support IMD protection and prevention.

Clinical significance of the UGT1A1*28 allele detection in HIV-infected patients.

INTRODUCTION: The UGT1A1*28 (rs8175347) polymorphism is associated with hyperbilirubinemia. The presence of 6 TA-repeats in the UGT1A1 gene promoter region corresponds to normal UGT1TA1 activity. A detection of 7 TA-repeats in hetero- or homozygous individuals [(TA)6/(TA)7 and (TA)7/(TA)7] is associated with lower UGT1TA1 activity, which may eventually result in the development of Gilbert syndrome and/or modified individual response to drugs metabolized by this enzyme. ATV contributes to the decreased levels of UGT1A1, which may lead to elevations of indirect bilirubin, jaundice and even to therapy discontinuation. We evaluated the prevalence of the UGT1A1*28 among HIV-infected patients and the dependence of the frequency and severity of AE during ATV treatment on individual genetic characteristics. MATERIALS AND METHODS: 47 HIV-infected patients was screen for UGT1A1 genotype and the presence of UGT1A1*28. All patients received ATV in the HAART regimen for 48 weeks. Changes in the total, direct and indirect bilirubin, ALT, AST, GGT and jaundice were evaluated. Statistical analysis was performed using Microsoft Office Excel for Windows XP Professional 2007 and Biostat. RESULTS: All patients were followed up in the AIDS Center (males 72.3%, median age 33 years, median CD4+ count-282 cells/µl (19.5%)). HBV/HCV was in 36.2% patients. Ten patients had risk factors that could affect bilirubin turnover (chronic cholecystitis, biliary dyskinesia, etc.). Genotype (TA)6/(TA)6 was found in 42.6% patients, (TA)6/(TA)7-42.6% and (TA)7/(TA)7-14.9%. Overall prevalence of UGT1A1*28 was 57.4%, and homozygous allele frequency was 14.9%. G3/4 of indirect bilirubin were detected in 36.2% patients [(TA)6/(TA)6 in 10-20%, (TA)6/(TA)7-25-40%, (TA)7/(TA)7-72-86%], and significant jaundice in 10.6% [80% with (TA)7/(TA)7]. The OR for hyperbilirubinemia>40 µmol/L in patients with heterozygous UGT1A1*28 was increased 3 times over patients without this allele (OR 3.07, 95% CI 1.54-4.6) and 34 times as compared with homozygotes (OR 33.9, 95% CI 31.45-36.35). The presence of additional risk factors increased the probability of G3/4 hyperbilirubinemia. No significant changes in the ALT, AST, and GGT levels were observed. CONCLUSIONS: The risk of severe hyperbilirubinemia during ATV treatment is minimal for patients without UGT1A1*28 and no more than one additional risk factor and for patients with UGT1A1*28 and no additional risk factors; patients with homozygous genotype UGT1A1*28 are at the highest risk.

Streptococcus pneumoniae serotype distribution in children in the Russian Federation before the introduction of pneumococcal conjugate vaccines into the National Immunization Program.

WHO recommends the inclusion of PCVs in childhood vaccination programs world-wide. Many countries including the Russian Federation are currently planning the inclusion of PCVs in their National Immunization Programs and, therefore, data on the pneumococcal serotype distribution is important to estimate the potential disease impact. Here we review eight recent epidemiological studies on the pneumococcal serotype distribution from Russia. Across all studies, serotypes 6B, 14, 19F and 23F were the most prevalent. Interestingly, serotype 3 was relatively common. Serotype 19A was prevalent among AOM, CAP and nasopharyngeal isolates and among antibiotic resistant isolates in all age groups. The differences in serotype coverage between PCV10 and PCV13 were up to 26%. Based on the current data on serotype distribution, a wide use of PCVs in Russia may lead to a significant reduction of the pneumococcal disease burden.