Nitric Oxide Synthase 2 Promoter Polymorphism Is a Risk Factor for Allergic Asthma in Children

Background and Objectives: In paediatric population, atopic asthma is associated with increased eosinophil counts in patients, that correlate with the airway inflammation measured by the concentration of nitric oxide in exhaled air (FeNO). As the FeNO level is a biomarker of atopic asthma, we assumed that polymorphisms in nitric synthases genes may represent a risk factor for asthma development. The purpose of this study was to analyse the association of NOS genetic variants with childhood asthma in the Polish population. Materials and methods: In study we included 443 children—220 patients diagnosed with atopic asthma and 223 healthy control subjects. We have genotyped 4 single nucleotide polymorphisms (SNP) from 3 genes involved in the nitric oxide synthesis (NOS1, NOS2 and NOS3). All analyses were performed using polymerase chain reaction with restriction fragments length polymorphism (PCR-RFLP). Results: We observed significant differences between cases and controls in SNP rs10459953 in NOS2 gene, considering both genotypes (p = 0.001) and alleles (p = 0.0006). The other analyzed polymorphisms did not show association with disease. Conclusions: According to our results, 5′UTR variant within NOS2 isoform may have an impact of asthma susceptibility in the population of Polish children. Further functional studies are required to understand the role of iNOS polymorphism in NOS2 translation and to consider it as a novel risk factor in childhood asthma. The next step would be to apply this knowledge to improve diagnosis and develop novel personalized asthma therapies.

The MUC5B Promoter Polymorphism Associates With Severe COVID-19 in the European Population

Background: Diversity in response on exposure to severe acute respiratory syndrome coronavirus 2 may be related to the innate immune response in the elderly. The mucin MUC5B is an important component of the innate immune response and expression levels are associated with the MUC5B promoter polymorphism, rs35705950. The high expressing T-allele is a risk allele for the non-infectious aging lung disease idiopathic pulmonary fibrosis (IPF). We investigated if MUC5B rs35705950 associates with severe COVID-19.Methods: In this retrospective candidate gene case-control study we recruited 108 Dutch patients (69% male, median age 66 years, 77% white) requiring hospitalization for COVID-19 (22% ICU stay, 24% died). For validation, genotypes were obtained from the UK-Biobank (n = 436, 57% male, median age 70 years, 27% died), for replication data from the severe COVID-19 GWAS group from Italy (n = 835) and Spain (n = 775) was used, each with a control cohort (n = 356,735, n = 1,255, n = 950, respectively). MUC5B association analysis was performed including adjustment for age and sex.Results: The rs35705950 T-allele frequency was significantly lower in Dutch white patients (n = 83) than in controls (0.04 vs. 0.10; p = 0.02). This was validated in the UK biobank cohort (0.08 vs. 0.11; p = 0.001). While age and sex differed significantly between cases and control, comparable results were obtained with age and sex as confounding variables in a multivariate analysis. The association was replicated in the Italian (p = 0.04), and Spanish (p = 0.03) case-control cohorts. Meta-analysis showed a negative association for the T-allele with COVID-19 (OR = 0.75 (CI: 0.67–0.85); p = 6.63 × 10−6).Conclusions: This study shows that carriage of the T-allele of MUC5B rs35705950 confers protection from development of severe COVID-19. Because the T-allele is a known risk allele for IPF, this study provides further evidence for the existence of trade-offs between optimal mucin expression levels in the aging lung.

Genetic modifiers of fetal hemoglobin affect the course of sickle cell disease in patients treated with hydroxyurea

The course of sickle cell disease (SCD) is modified by polymorphisms boosting fetal hemoglobin (HbF) synthesis. However, it has remained an open question how these polymorphisms affect patients who are treated with the HbF-inducing drug hydroxyurea/hydroxycarbamide. The German SCD registry offers the opportunity to answer this question, because >90% of patients are treated according to national guidelines recommending the use of hydroxyurea in all patients above 2 years of age. We analyzed the modifying effect of HbF-related genetic polymorphisms in 417 patients with homozygous SCD >2 years who received hydroxyurea. HbF levels were correlated with higher total hemoglobin levels, lower rates of hemolysis, a lower frequency of painful crises and of red blood cell transfusions. The minor alleles of the polymorphisms in the γ-globin promoter (rs7482144), BCL11A (rs1427407) and HMIP (rs66650371) were strongly associated with increased HbF levels. However, these associations did not translate into lower frequencies of vasoocclusive events that did not differ between patients either carrying or not carrying the HMIP and BCL11A polymorphisms. Patients on hydroxyurea carrying the γ- globin promoter polymorphism demonstrated substantially higher hemoglobin levels (p

Association between Interleukin-10 promoter polymorphism with type 2 Diabetes mellitus

Type 2 diabetes mellitus is a multifactorial illness triggered by a complicated interplay of various genetic variants with various environmental variables. The quantity of replicated common genetic variants associated with type 2 diabetes mellitus has increased rapidly with the recent genome-wide association (GWA) research. Major health issue in the public are type 2 diabetes mellitus (T2DM) is common throughout the world. Diabetes mellitus incidence is growing and is anticipated to affect 300 million individuals by 2025. Diabetes has been suggested to alter patterns of cytokine expression as an immune-dependent illness. Insulin resistance (IR) is a disease that results in less than anticipated biological impact of a specified insulin concentration. Insulin resistance and insulin secretion decreased are both defined pathophysiology of T2DM. One of the most alarming health issues of the 21st century is the spread of diabetes around the globe. Our goal in this study was to identify the role of IL-10 polymorphism in T2DM patients. The average age of 60 median patients with type 2 diabetes mellitus (31 males and 29 females) +-SD (45.91667 +-16.08799), fasting blood sugar (FBS) is +-SD (184.25 +-57.76387), hypertension (35 positive/25 negative) and 60 non-diabetic controls (32 males and 28 females) is +- SD (47.31667 +-15.13722). The group (T2DM patients and their control) had not a substantial distinction (P=0.33) and in each group (CC, TT, CT) there was a comparison between IL-10 gene polymorphism. T2DM patients and healthy individuals are not associated with the polymorphism of the gene IL-10 (SNP rs 3021097 (C/T). Keywords: Insulin, Diabetes Mellitis Type 2, Polymorphism, Interleukin-10, Genotype frequencies.