Association between interleukin-6-174G/C gene polymorphism and asthma severity: exploring the role of total serum IgE, blood eosinophils, and FeNO as markers of type 2 inflammation.

BACKGROUND: While a connection has been established between serum interleukin-6 (IL-6) levels and the IL-6 gene (- 174G/C) polymorphism in allergic diseases such as asthma, its specific association with severe asthma remains unexplored. This study examined the relationship between the IL-6 (- 174G/C) gene polymorphism and mild and severe asthma, focusing on its influence on type 2 inflammation. METHODS: Our study comprised 98 patients with mild asthma and 116 with severe asthma. Additionally, we recruited 121 healthy participants to serve as controls for comparative analyses. The IL-6 gene (- 174G/C) polymorphism was assessed utilizing the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: In our study, the risk of mild asthma exhibited a significant fourfold increase in individuals with the GG genotype pattern compared to healthy controls, yielding an odds ratio (OR) of 4.4 (p < 0.001). Conversely, we found no significant correlation between the IL-6 - 174G/C gene polymorphism and severe asthma when compared to the healthy control group. However, a noteworthy pattern emerged when we compared subgroups of mild and severe asthma. The risk of severe asthma increased fivefold in individuals with the GC polymorphism pattern, with an OR of 4.99 (p < 0.001), while the likelihood of mild asthma showed a similar fourfold increase with the GG polymorphism pattern, OR = 4.4 (p < 0.001). Consequently, we observed a significantly higher frequency of the C allele in patients with severe asthma, whereas the G allele was more prevalent in individuals with mild asthma (p = 0.05). Additionally, the correlation between markers of type 2 inflammation and the dominant model of the IL-6 gene -174G/C polymorphism (CC + CG vs GG) revealed a significant increase in total serum immunoglobulin E (IgE), Blood Eosinophil Counts (BEC), and Fractional Exhaled Nitric Oxide (FeNO) levels in asthmatic patients with the CC + CG gene pattern compared to those with GG, with p-values of 0.04, 0.03, and 0.04, respectively. Furthermore, after adjusting for other risk factors, the likelihood of developing severe asthma increased from fourfold to eightfold, with an OR of 8.12 (p = 0.01) with (CC + CG) gene pattern. Other predictors for severe asthma included older age and childhood-onset disease (OR = 1.13 and 19.19, p < 0.001). Allergic rhinitis (AR) and nasal polyps (NP) also demonstrated a substantial association with an increased risk of severe asthma, with odds ratios of 5 and 32.29 (p = 0.01 and < 0.001), respectively. Additionally, elevated Body Mass Index (BMI), BEC, and FeNO were linked to severe asthma, with ORs of 1.11, 1.00, and 1.04, respectively (p = 0.04, 0.05, and 0.001). CONCLUSION: This study illuminated the intricate relationship between the IL-6 gene polymorphism, type 2 inflammation markers, and diverse risk factors in shaping asthma severity. As a significant association between the GG polymorphism of the IL-6 gene (- 174G/C) and mild asthma was found, while possessing at least one C allele, whether in a homozygous (CC) or heterozygous (CG) combination, independently predicts the likelihood of severe asthma.

Tumor necrosis factor alpha gene polymorphism affects the pattern of idiopathic nephrotic syndrome in Kuwaiti Arab children.

OBJECTIVES: TNF-α is a pro-inflammatory cytokine that has been implicated in many inflammatory diseases, but its association with idiopathic nephrotic syndrome (INS) is poorly understood. This study looked for an association of TNF-α gene polymorphisms with INS, as well as its effect on steroid responsiveness among Kuwaiti Arab children. METHODS: Genotypes of the TNF-a gene polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism in 151 INS Kuwaiti Arab patients and 64 age and sex-matched controls. Clinical data of all subjects were reviewed. RESULTS: The heterozygous AG genotype was detected in 8.6% of INS patients compared 23.4% of the controls (p < 0.01). Comparing steroid responsiveness, AA genotype was significantly more common in steroid-sensitive nephrotic syndrome (SSNS) cases than steroid-resistant nephrotic syndrome (SRNS) patients (p = 0.001). However, AG genotype was significantly more common in SRNS patients compared to the SSNS cases (p = 0.001). No difference was found between these two subgroups in the GG genotype frequency. CONCLUSION: AG genotype of TNF-a gene polymorphisms may be considered a suitable marker for INS disease among Kuwaiti children. Both AA and AG genotypes may be useful in predicting steroid responsiveness among these cases of Arab ethnicity. The findings might open the era for the use of genetic markers in the early treatment of NS.

Unveiling a Biomarker Signature of Meningioma: The Need for a Panel of Genomic, Epigenetic, Proteomic, and RNA Biomarkers to Advance Diagnosis and Prognosis.

Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation into advanced grades classified by World Health Organization (WHO) into Grades 1 to 3. Meningiomas' tremendous variability in tumor behavior and slow growth rates complicate their diagnosis and treatment. A deeper comprehension of the molecular pathways and cellular microenvironment factors implicated in meningioma survival and pathology is needed. This review summarizes the known genetic and epigenetic aberrations involved in meningiomas, with a focus on neurofibromatosis type 2 (NF2) and non-NF2 mutations. Novel potential biomarkers for meningioma diagnosis and prognosis are also discussed, including epigenetic-, RNA-, metabolomics-, and protein-based markers. Finally, the landscape of available meningioma-specific animal models is overviewed. Use of these animal models can enable planning of adjuvant treatment, potentially assisting in pre-operative and post-operative decision making. Discovery of novel biomarkers will allow, in combination with WHO grading, more precise meningioma grading, including meningioma identification, subtype determination, and prediction of metastasis, recurrence, and response to therapy. Moreover, these biomarkers may be exploited in the development of personalized targeted therapies that can distinguish between the 15 diverse meningioma subtypes.

Interleukin-4 (C590T) Gene Polymorphism in Association with Asthma Severity.

Background: A significant link between T allele of the IL-4 (C590T) gene and developing asthma in some populations was reported. However, no study discussed the link between IL-4 (C590T) gene polymorphism and asthma severity groups (mild and severe). This study investigated the link between IL-4 gene variation and asthma severity. Methods: The study included 215 asthmatic patients, of which 102 had mild asthma, and 126 participants were healthy controls. A previously published polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify various IL-4 (C590T) gene polymorphism genotypes. Results: The T allele frequency was higher in mild asthma (p=0.002) but not in severe asthma (p=0.12) compared to controls. In mild asthma, the CT genotype and (CT+TT versus CC) increased the likelihood of asthma threefold (p<0.001, 0.001). However, no significant association with severe asthma was found in either genetic model. Stratification analysis showed that the C allele and CC genotype increased the risk of severe asthma (p=0.01). The recessive genetic model indicated a decrease in the risk of severe asthma (OR=0.5, p=0.01) in the non-adjusted regression analysis. Adjusting for age, sex, and other risk factors revealed that the IL-4 gene polymorphism did not influence the risk of severe asthma (OR=0.92, p=0.80); however, being an elderly female with a history of childhood-onset disease and associated nasal polyp (NP) increased the likelihood of severe asthma, OR=1.08, 2.01, 2.36, 8.42; p<0.001, 0.05, 0.05, <0.001, respectively. Conclusion: The T allele and CT genotype in the co-dominant genetic model and the (CT+TT) genotype in the recessive model were found to have a higher likelihood of developing mild asthma but not severe asthma; severe asthma was found to be higher in elderly females with a history of childhood-onset disease and associated nasal polyps.

Resveratrol-Mediated Regulation of Mitochondria Biogenesis-associated Pathways in Neurodegenerative Diseases: Molecular Insights and Potential Therapeutic Applications.

Neurodegenerative disorders include different neurological conditions that affect nerve cells, causing the progressive loss of their functions and ultimately leading to loss of mobility, coordination, and mental functioning. The molecular mechanisms underpinning neurodegenerative disease pathogenesis are still unclear. Nonetheless, there is experimental evidence to demonstrate that the perturbation of mitochondrial function and dynamics play an essential role. In this context, mitochondrial biogenesis, the growth, and division of preexisting mitochondria, by controlling mitochondria number, plays a vital role in maintaining proper mitochondrial mass and function, thus ensuring efficient synaptic activity and brain function. Mitochondrial biogenesis is tightly associated with the control of cell division and variations in energy demand in response to extracellular stimuli; therefore, it may represent a promising therapeutic target for developing new curative approaches to prevent or counteract neurodegenerative disorders. Accordingly, several inducers of mitochondrial biogenesis have been proposed as pharmacological targets for treating diverse central nervous system conditions. The naturally occurring polyphenol resveratrol has been shown to promote mitochondrial biogenesis in various tissues, including the nervous tissue, and an ever-growing number of studies highlight its neurotherapeutic potential. Besides preventing cognitive impairment and neurodegeneration through its antioxidant and anti-inflammatory properties, resveratrol has been shown to be able to enhance mitochondria biogenesis by acting on its main effectors, including PGC-1α, SIRT1, AMPK, ERRs, TERT, TFAM, NRF-1 and NRF-2. This review aims to present and discuss the current findings concerning the impact of resveratrol on the machinery and main effectors modulating mitochondrial biogenesis in the context of neurodegenerative diseases.

Impact of Smoking on COVID-19 Symptoms in Non-Vaccinated Patients: A Matched Observational Study from Qatar.

Purpose: Predisposition to acute illness from COVID-19 is suggested to correlate with cigarette smoking as it augments the risk of developing cardiovascular and respiratory illnesses, including infections. However, the effects of smoking on COVID-19 symptoms are not well described and controversial. In this study, we aim to explore the associations between smoking and COVID-19 symptoms. Subjects and Methods: A cross-sectional study using the Ministry of Public Health (MoPH), Qatar database was administered to a Qatari population with confirmed COVID-19 disease who filled in pre-defined phone-call questionnaire between 27th February 2020 and 31st December 2020. We analyzed 11,701 non-vaccinated COVID-19 individuals (2952 smokers and 8749 non-smokers) with confirmed RT-PCR test results. The association of smoking and the presence of symptoms as well as patient characteristics was calculated using Pearson's Chi-square and Fisher's exact tests, adjusting for potential covariates. Results: Compared with the non-smokers, symptomatic COVID-19 infection is significantly higher in smokers. In addition, we found fever as the most common symptom developed in COVID-19 patients followed by cough, headache, muscle ache, and sore throat. As compared to other symptoms, association of smoking with chills and abdominal pain was less evident (P < 0.05 and P < 0.001, respectively). However, both groups showed similar rates of developing cough. Conclusion: In conclusion, smoking is associated with COVID-19 symptoms frequency in non-vaccinated patients; nevertheless, further investigations are necessary to understand the mechanism of this association which could generate new targets for the management of COVID-19 in smoker patients.

Association of angiotensin-converting enzyme (ACE) gene insertion-deletion polymorphism with spondylarthropathies.

Low back pain (LBP) is a common medical problem. Interaction between genetic and environmental factors predisposes individuals to LBP even at an early age. Inflammatory back pain or spondylarthropathies include ankylosing spondylitis (AS), psoriatic arthritis (PSA), reactive arthritis enteropathic and undifferentiated arthropathies. Angiotensin-converting enzyme (ACE) plays an important role in circulatory homeostasis, physiology of vasculature and inflammation. The insertion-deletion (I/D) polymorphism of the ACE gene has been shown to determine the plasma and tissue levels of ACE especially in the synovial fluid. The aim of this study was to investigate an association between ACE gene I/D polymorphism and inflammatory back pain (spondylarthropathies) secondary to ankylosing spondylitis (AS), psoriatic arthritis, inflammatory bowel disease and undifferentiated spondylarthropathies. The prevalence of ACE gene I/D polymorphism genotypes was determined in 63 patients with inflammatory back pain by polymerase chain reaction (PCR) and compared with that in 111 healthy controls. Of the 63 patients studied, 45 (71.4%) were with AS, 13 (20.6%) were with PSA, 4 (6.3%) were with reactive arthropathy and 1 (1.6%) manifested undifferentiated arthropathy. There were 43 males and 20 females. Mean age of patients was 39.0+/-11.36 years, age at onset of spondylarthropathy was 27.7+/-7.49 years and disease duration was 10.3+/-7.74 months. The controls were selected to match with the patients group in terms of gender ratio, age and ethnicity. The ACE gene polymorphism showed an overall significant difference between patients and controls (p=0.050). When the ID and II genotype frequency was combined and compared with that for DD genotype amongst patient and control groups, a considerably higher incidence was detected for ID and II genotypes than the DD genotype in spondylarthropathy patients compared to that in the controls (p=0.036). This study showed a significant association of the I-allele of ACE gene I/D polymorphism with spondylarthropathy in Kuwaiti Arabs.