Influence of light at night on allergic diseases: a systematic review and meta-analysis.

BACKGROUND: Allergic diseases impose a significant global disease burden, however, the influence of light at night exposure on these diseases in humans has not been comprehensively assessed. We aimed to summarize available evidence considering the association between light at night exposure and major allergic diseases through a systematic review and meta-analysis. METHODS: We completed a search of six databases, two registries, and Google Scholar from inception until December 15, 2023, and included studies that investigated the influence of artificial light at night (ALAN, high vs. low exposure), chronotype (evening vs. morning chronotype), or shift work (night vs. day shift work) on allergic disease outcomes (asthma, allergic rhinitis, and skin allergies). We performed inverse-variance random-effects meta-analyses to examine the association between the exposures (ALAN exposure, chronotype, or shiftwork) and these allergic outcomes. Stratification analyses were conducted by exposure type, disease type, participant age, and geographical location along with sensitivity analyses to assess publication bias. RESULTS: We included 12 publications in our review. We found that exposure to light at night was associated with higher odds of allergic diseases, with the strongest association observed for ALAN exposure (OR: 1.88; 95% CI: 1.04 to 3.39), followed by evening chronotype (OR: 1.35; 95% CI: 0.98 to 1.87) and exposure to night shift work (OR: 1.33; 95% CI: 1.06 to 1.67). When analyses were stratified by disease types, light at night exposure was significantly associated with asthma (OR: 1.62; 95% CI: 1.19 to 2.20), allergic rhinitis (OR: 1.89; 95% CI: 1.60 to 2.24), and skin allergies (OR: 1.11; 95% CI: 1.09 to 1.91). We also found that the association between light at night exposure and allergic diseases was more profound in youth (OR: 1.63; 95% CI: 1.07 to 2.48) than adults (OR: 1.30; 95% CI: 1.03 to 1.63). Additionally, we observed significant geographical variations in the association between light at night exposure and allergic diseases. CONCLUSIONS: Light at night exposure was associated with a higher prevalence of allergic diseases, both in youth and adults. More long-term epidemiological and mechanistic research is required to understand the possible interactions between light at night and allergic diseases.

A review on aero-allergen induced allergy in India.

Allergic diseases such as bronchial asthma, rhinitis and eczema are an important public health issue globally in 21st century. Their prevalence and impact in India is high, in terms of total numbers of people affected. Due to diverse climate and lifestyle, the Indian population is exposed to a rich and varied range of aerobiological particles. In the last two decades in India, 83 pollens, 34 fungi, six dust mite and 19 insect species were reported as allergenic, often contributing to heavy allergenic exposure in indoor and outdoor environments. There are currently few practitioners who offer allergy diagnosis and treatment in India, but there is active basic and molecular research aiming to improve the health of allergic patients. This review explores the field of aero-allergy in India during the last two decades, with special emphasis on prevalence across various centres and relevant scientific advances such as genetic associations and new therapeutics. This review will be helpful for clinicians to select aero-allergens for sensitisation testing in patients suffering from symptoms in different regions of India, and to support patients undertaking prophylaxis of allergic symptoms in India according to local environmental conditions. This study also helps to define patient selection for allergy testing and the role of test results in guiding allergic disease management in the Indian context. Finally, we summarize genetic findings relevant to aero-allergy in India and discuss the development of novel therapeutics for investigation and management of aero-allergy in India.

Allergic rhinitis in India.

India is the home of nearly 20% of the global population with 1.35 billion people. Of all non-communicable diseases, allergic diseases such as allergic rhinitis (AR) and asthma appear to have increased in India over the past decades. Approximately 22% of adolescents currently suffer from AR in India. However, owing to the lack of adequate epidemiological studies in India, particularly in rural and suburban areas, this number may misrepresent the true burden of this disease. While the risk factors for AR are mainly environmental exposures or genetic factors, several new environmental, social, and behavioural risk factors such as the presence of dumpsters near residences, movement of vehicles near homes, and exposure to artificial light at night have been found to be associated with AR. However, despite international guidelines, the diagnosis and management of AR in India are often suboptimal, for multiple reasons such as the lack of specialized training in allergy and immunology among Indian clinicians, the lack of diagnostic facilities, and the high cost of medications. This review aims at highlighting the current scenario of AR in India and how it differs from the rest of the world. It also highlights the need for developing a strategic approach to enhance the quality of care for allergic diseases by upgrading education and training for healthcare professionals, creating awareness among clinicians and patients, and involving stakeholders and policymakers in making treatments accessible and affordable to patients.

Allergic diseases in India - Prevalence, risk factors and current challenges.

Epidemiological studies have shown a rise in the prevalence of allergic diseases in India during the last two decades. However, recent evidence from the Global Asthma Network study has observed a decrease in allergic rhinitis, asthma and atopic dermatitis in children. Still, with a population over 1.3 billion, there is a huge burden of allergic rhinitis, asthma and atopic dermatitis, and this is compounded by an unmet demand for trained allergy specialists and poor health service framework. There is wide variation in the prevalence of allergic diseases between different geographical locations in India, and the reasons are unclear at present. This may at least in part be attributable to considerable heterogeneity in aero-biology, weather, air pollution levels, cultural and religious factors, diet, socioeconomic strata and literacy. At present, factors enhancing risks and those protecting from development of atopy and allergic diseases have not been well delineated, although there is some evidence for the influence of genetic factors alongside cultural and environmental variables such as diet, exposure to tobacco smoke and air pollution and residence in urban areas. This narrative review provides an overview of data from India regarding epidemiology, risk factors and genetics and highlights gaps in evidence as well as areas for future research.

Assessment of Co-Sensitization between Pollen and Food Allergen Sources among Bengali Population, West Bengal, India.

INTRODUCTION: Secondary food allergies due to cross-reactivity between pollen and food allergens are a significant health burden in India. Prevalence of cross-reactivity varies by region, and particularly in West Bengal, it remains unexplored. The present study investigated sensitivities of pollen-related food allergy (PFA) patients of West Bengal by empirically determining co-sensitization patterns. METHODS: The present study retrospectively analysed 1,310 pollen-allergic (PA) patients from the Allergy and Asthma Research Centre, West Bengal. A questionnaire survey was performed to record patients' demographic and clinical features and categorized into seasonal and perennial ones. All patients were subjected to the skin prick test and specific IgE for evaluation of sensitivity against 16 pollen and 16 food allergens. Co-relation and principal component analysis (PCA) was performed to determine co-sensitivity. RESULTS: Seasonal allergic patients were comparatively higher than perennial ones. PFA patients were mostly sensitive to eggplant (n = 387), while Azadirachta indica (n = 341) was predominant sensitizer among pollen allergen sources. Cynodon dactylon showed maximum significant positive correlation with banana, orange, peanut, pineapple, cucumber, eggplant, potato, tomato, and wheat. In the seasonal group, Cynodon dactylon-specific IgE in PFA patients (median = 4.60 kU/L) was significantly higher from that of PA ones (median = 3.44 kU/L). Among 32 allergens tested, 27 were placed in first two dimensions of the PCA biplot. CONCLUSION: The present study established that co-sensitivity between pollen and food allergen sources were predominant in allergic patients of West Bengal. The co-sensitization patterns among unrelated allergen sources may be due to possible expression of biologic cross-reactivity to similar allergens.

Kinetics of Covid-19 antibodies in terms of titre and duration among healthcare workers: A longitudinal study.

Background Most individuals with Covid-19 infection develop antibodies specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the dynamics of these antibodies is variable and not well-studied. We aimed to determine the titres of naturally acquired antibodies over a 12-week follow-up. Methods We recruited healthcare workers who had tested positive on a specific quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for SARS-CoV-2, and then tested for the presence of immunoglobulin G (IgG) antibody against the same virus at baseline and again at 6 and 12 weeks. The antibody titre was determined by a semi-quantitative assay based on signal/cut-off ratio. Healthcare workers with antibody positivity were divided into those with high titre (ratio ≥12) and low titre (<12). Their demographic details and risk factors were surveyed through a Google form and analysed in relation to the antibody titres at three time-points. Results Of the 286 healthcare workers, 10.48% had high antibody titres. Healthcare workers who had tested positive by qRT-PCR and those who had received the Bacille Calmette-Guérin (BCG) vaccination or other immune-boosters had a higher frequency of high antibody titres. While there was a significant decline in antibody titres at 6 and 12 weeks, 87.46% of individuals positive for IgG antibody persisted to have the antibody even at 12 weeks. Conclusion Healthcare workers who tested positive for SARS-CoV-2 on qRT-PCR had a high positivity for the specific antibody, which continued to express in them even at 12 weeks. Further follow-up is likely to enhance our understanding of antibody kinetics following SARS-CoV-2 infection.

Association of HLA-DQ and IL13 gene variants with challenge-proven shrimp allergy in West Bengal, India.

Little is known about genetic factors and mechanisms underlying shrimp allergy. Genome-wide association studies identified HLA class-II and IL13 genes as highly plausible candidates for shrimp allergy. The present study was designed to investigate potential associations of HLA-DQ rs9275596, IL13 rs20541, and IL13 rs1800925 polymorphisms with challenge-proven shrimp allergy using the data from 532 people of West Bengal, India; selected on basis of positive skin prick test, elevated specific IgE and medical history. Risk genotypes, i.e., HLA-DQ rs9275596 CC, IL13 rs20541 AA, and IL13 rs1800925 TT, were found to be significantly associated with challenge positive shrimp allergy (P = 0.04, 0.01, and 0.03, respectively). Distribution of genotypes for HLA-DQ and IL13 polymorphisms in allergic and control subjects showed significant difference between younger (20-40 years) and older (> 40 years) age group (P = 0.006). Risk genotypes significantly associated with elevated shrimp-specific IgE. IL13 TA haplotype significantly associated with shrimp allergy and elevated specific IgE (P = 0.02). Synergistic effect of IL13 TA haplotype-HLA-DQ rs9275596 CC genotype interaction significantly elevated specific IgE (P = 0.03). The present study suggests that HLA-DQ and IL13 polymorphisms pose major risk for shrimp allergic patients in West Bengal, India and thus could be helpful for early target-specific therapeutic intervention in near future.

Association of the STAT6 rs3024974 (C/T) Polymorphism with IgE-Mediated Food Sensitization among West Bengal Population in India.

INTRODUCTION: Genetic polymorphisms associated with IgE-mediated food sensitization have been a robust area of research for decades. A genome-wide search for susceptible loci regulating the IgE response (atopy) identified the candidate gene STAT6, which is important in the context of food allergic manifestations. OBJECTIVE: The present study was designed to investigate the sensitization of West Bengal population against some common allergenic food items and to study the role of the STAT6 gene polymorphism in elevating food-specific IgE levels among sensitized individuals. METHODS: Skin prick test was performed for 6 food items among 501 patients (126 children, 85 adolescents, and 290 adults)from West Bengal, India. Among them, 165 patients were selected for measurement of total IgE and food-specific IgE levels along with 165 controls. Finally, the STAT6 (rs3024974 (C/T) polymorphism was genotyped in 139 cases and control subjects. RESULTS: Shrimp was identified as a dominant food allergen in adolescents and adults, whereas milk sensitization was highest in children. Food-sensitized patients with onset during childhood had significantly higher total IgE levels compared to patients with onset during adulthood (p < 0.00001). The frequency of the rs3024974 CC genotype in both cases and control subjects (55.40 and 46.76%, respectively) was higher than that of CT or TT. Patients with childhood onset bearing the CC genotype had significantly higher specific IgE levels in comparison to those with adult onset (p = 0.001). CONCLUSION: Food sensitization has a genetic background and the rs3024974 polymorphism is associated with susceptibility and reaction severity in food-sensitized patients in West Bengal population in India.

Pediatric allergic diseases in the Indian subcontinent-Epidemiology, risk factors and current challenges.

INTRODUCTION: India is low-middle-income country (LMIC) with a population of 1.3bn, comprising about 20% of the global population. While the high-income Western countries faced an "allergy epidemic" during the last three decades, there has been a gradual rise in prevalence of allergic diseases in India. METHODS: Narrative review. RESULTS AND DISCUSSION: Allergic diseases occur as a consequence of a complex interplay between genetic and environmental factors. There are multiple contrasting determinants that are important to consider in India including high levels of air pollution, in particular PM2.5 due to burning of fossil fuels and biomass fuels, diverse aero-biology, tropical climate, cultural and social diversity, religious beliefs/myths, linguistic diversity, literacy level, breastfeeding and weaning, diet (large proportion vegetarian), and high incidence rates of TB, HIV, malaria, filariasis, parasitic infestations, and others, that not only shape the immune system early in life, but also impact on biomarkers relevant to allergic diseases. India has a relatively weak and heterogeneous healthcare framework, and allergology has not yet been recognized as an independent specialty. There are very few post-graduate training programs, and allergic diseases are managed by primary care physicians, organ-based specialists, and general pediatricians. Adrenaline auto-injectors are not available, there is patient unaffordability for inhalers, nasal sprays, and biologics, and this is compounded by poor compliance leading to 40%-50% of asthmatic children having uncontrolled disease and high rates of oral corticosteroid use. Standardized allergen extracts are not available for skin tests and desensitization. This article provides a critical analysis of pediatric allergic diseases in India.

Risk Benefit Analysis in Reference to use of LMWH in COVID-19.

Venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) are frequent cardiovascular and/or respiratory complications among hospitalized patients of COVID-19 infection. A relatively high mortality of severe coronavirus disease 2019 (COVID-19) is worrying, and the application of heparin in COVID-19 has been assessed and recommended with some expert consensus because of the risk of DIC and venous thromboembolism. However, "Risk Benefit Analysis" on the aspect of safety in using low molecular weight heparin (LMWH) in COVID-19 patients for thrombosis prophylaxis has been explained below with a few case studies and detailed information from various clinical evidence. COVID-19 infection has been associated with inflammation and a prothrombotic state, with increase in fibrin, fibrin degradation products, fibrinogen, and D-dimers. Heparin treatment including unfractionated and low molecular weight heparin appears to be associated with better prognosis in severe COVID-19 patients with coagulopathy. Major studies since the onset of this pandemic, found better prognosis in severe COVID-19 patients meeting SIC criteria or with markedly elevated D-dimer, by approaching thrombosis prophylaxis with LMWH.

T11TS immunotherapy augments microglial and lymphocyte protective immune responses against Cryptococcus neoformans in the brain.

Cryptococcus neoformans, the encapsulated yeast acquired through inhalation, remains localized in lungs, but harbours the CNS in immunocompromised individuals. Several treatment regimes have failed combating this disease totally, but long-term usage of drugs leads to organ damage. As T11-target structure (T11TS) has documented profound immune potentiation, we aimed to investigate the role of microglia, pivotal immune cells of brain in ameliorating cryptococcosis, with T11TS immunotherapy. Murine model with C neoformans infection was prepared by intraperitoneal injection and the brains of rats examined 7 days post-infections for histopathology by PAS and Alcian blue staining corroborated with organ fungal burden evidencing restorative T11TS action on Cryptococcal meningitis. Immunotherapy with three doses of T11TS, a CD2 ligand, in C neoformans infected rats, upregulates toll-like receptors 2, -4 and -9 of microglia, indicating increased phagocytosis of the fungus. Flowcytometric analysis revealed increased numbers of T11TS treated brain infiltrating CD4+ and CD8+ T-lymphocytes along with increased MHC I and MHC II on microglia, activating the infiltrating lymphocytes aiding the killing mechanism. Present study also indicated that T11TS increased production of Th1 inflammatory cytokines conducive to fungal elimination while the inhibitory Th2 cytokines were dampened. This preclinical study is first of its kind to show that T11TS effected profound immune stimulation of microglial activity of C neoformans infected rats eradicating residual fungal burden from the brain and can be a useful therapeutic strategy in fighting against this deadly disease.

Sensitization to Common Aeroallergens in the Atopic Population of West Bengal, India: An Investigation by Skin Prick Test.

BACKGROUND: Aeroallergen sensitization is increasing worldwide. The optimal management of allergic disease requires the identification of the allergic sensitivities of the patient. Complete data of offending aeroallergens are scant from West Bengal, India. Hence, we employed a retrospective analysis of an atopic population of West Bengal to investigate the rate of sensitivity toward common aeroallergens including pollens, molds and house dust mites. OBJECTIVES: The aim of the present study was to evaluate the profile of skin prick test (SPT) reactivity of an atopic population of eastern India. METHODS: The prevalence aeroallergen sensitization was investigated by SPT along with a questionnaire survey of patients who visited the Allergy and Asthma Research Center of West Bengal, India, from June 2016 to May 2018. Patients were categorized according to the demographic (age, gender) and clinical aspects. Statistical tests were applied to differentiate between age and gender of the sufferers. RESULTS: 524 out of 605 patients exhibited a positive SPT response toward one or more aeroallergens tested. One-way ANOVA following Tukey's post hoc test reveals the age group of 15-40 years was more sensitized than that of < 15 years and no male-female discrimination was found using the paired t test. House dust mites, namely Dermatophagoides pteronyssinus and Dermatophagoides farinae, elicited most significant SPT results (80.34 and 84.92%, respectively) followed by Cocos (73.28%) and Azaridacta (57.25%) pollen. The most sensitive mold was Alternaria alternata (26.9%). Allergic rhinitis, bronchial asthma and atopic dermatitis were recorded as the common symptoms. Other influencing factors were family history, nature and season/time of onset and house conditions. CONCLUSION: Following the increasing trend, house dust mite sensitization still held the dominance like in any other Indian population reported earlier. This study would pave the way to construct a standard and minimal SPT panel for the atopic patients of eastern India.

T11TS repress gliomagenic apoptosis of bone marrow hematopoietic stem cells.

Combating gliomagenic global immunosuppression is one of the emerging key for improving prognosis in malignant glioma. Apoptosis plays a pivotal role within the adult hematopoietic system particularly in regulating the cells of immune system. Gliomagenic regulation of apoptotic mediators within bone marrow milieu has not been elucidated. We previously demonstrated that administration of membrane glycopeptides T11 target structure (T11TS) not only rejuvenate bone marrow hematopoietic stem cells (BMHSCs) from glioma mediated hibernation by inhibiting gliomagenic overexpression of Ang-1/Tie-2 but also stimulate glioma mediated diminution of expression CD34, c-kit, and Sca-1 markers. In the present study, we investigated the impact of glioma on apoptotic signaling cascades of BMHSCs and consequences following T11TS therapy. Bone marrow smear and Annexin V staining confirm gliomagenic acceleration of apoptotic fate of BMHSCs whereas T11TS treatment in glioma-bearing rats disrupted apoptosis of BMHSCs. Flowcytometry, immunoblotting, and immunofluorescence imagining results revealed multi potent T11TS not only significantly downregulates gliomagenic overexpression of Fas, Fas L, Bid, and caspase-8, the pro-apoptotic extrinsic mediators but also strongly inhibits cytosolic release of cytochrome-c, Apf-1, and Bax to deactivate gliomagenic caspase-9, 3 the key intrinsic apoptotic mediators followed by up modulation of anti-apoptotic Bcl-2 in glioma associated HSCs. T11TS is also able to diminish the perforin-granzyme B mediated apoptotic verdict of BMHSCs during gliomagenesis. The anti-apoptotic action of T11TS on glioma associated BMHSCs provide a crucial insight into how T11TS exerts its immunomodulatory action against glioma mediated immune devastation.

Exposure to heavy metals alters the surface topology of alveolar macrophages and induces respiratory dysfunction among Indian metal arc-welders.

BACKGROUND: Despite the available clinico-epidemiological evidence of heavy metal-associated respiratory health hazards among metal arc-welders, experimental confirmation of such an association is lacking. METHODS: In this study, we recruited 15 metal arc-welders and 10 referent workers without direct exposure. We assessed respiratory health through a questionnaire and spirometry; estimated manganese, nickel and cadmium levels in blood, urine and induced sputum; performed differential counts of sputum leucocytes and measured plasma malondialdehyde (MDA). We used atomic force and scanning electron microscopy to assess the physical property of the alveolar macrophages (AMs) obtained from induced sputum and analysed cell surface deposition of heavy metals using energy dispersion X-ray analysis (EDX). Sputum cellular DNA damage was assessed by DNA-laddering assay. RESULTS: There was a higher body burden of manganese and nickel in the metal arc-welders than the referents. Among major spirometric indices, only the forced mid-expiratory flow rates (FEF25-75) were reduced in the welders compared with the referents (63.4 ± 14.7 vs. 89.2 ± 26.7, p < 0.01); this reduction was associated with both heavy metal levels (ß: -41.8, 95% CI: -78.5% to -5.1%) and plasma MDA (-0.37; -0.68 to -0.06). In metal arc-welders, significant physical and morphological changes were observed in AMs through microscopic evaluation while EDX analyses demonstrated higher deposition of heavy metals on the AM cell surface than the referents. We also observed a higher degree of DNA damage in the sputum cells of the exposed workers than the referents. CONCLUSION: Heavy metal exposure-induced adverse respiratory effects among metal arc-welders are mediated through haematological and cytological interactions.

Effectiveness of budesonide formoterol fixed-dose combination MDI in reducing cough symptoms in COVID-19 patients: A real-world evidence study.

Background: Cough is a wearisome and exasperating symptom affecting the daily life of the infected patient. Cough due to coronavirus disease 2019 (COVID-19) causes excessive morbidity in human populations globally. Apart from the morbidity associated with cough, it also enhances the transmission of this viral infection through droplets. Therefore, curbing cough is crucial to limit its spread. Patients often administer over-the-counter products and antitussive agents, which have no proven benefit. The present study was undertaken to find out if cough associated with COVID-19 and other indicative clinical outcomes is alleviated with a budesonide/formoterol fixed-dose combination (FDC) metered-dose inhaler (MDI). Materials and Methods: A prospective observational study was conducted in mild COVID-19 patients who presented with a cough score ≥8 at presentation. Patients who were initiated on ICS-LABA MDI were observed as group A and those who were not initiated on MDI were observed as Group B. Cough symptom score (at baseline and on day 3 and day 7), the incidence of hospital admission and/or death, and need for mechanical ventilation were documented. Prescribing patterns of anti-cough medications were also noted and analysed. Results: Compared to group B, a higher mean cough score reduction was noted for group A patients at day 3 and day 7 when compared to the baseline, and this was significant at P < 0.001. A significant negative correlation was also observed between mean latency of MDI initiation from the symptom onset and mean cough score reduction. Analysis of the proportion of patients prescribed medications to treat cough showed that overall, 10.78% did not require these, with a greater proportion in group A compared to group B. Conclusion: Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 who were treated with ICS-LABA MDI along with usual care benefitted significantly in terms of symptom reduction compared to usual care.

In silico analysis of single nucleotide polymorphism (rs34377097) of TBXA2R gene and pollen induced bronchial asthma susceptibility in West Bengal population, India.

Introduction: Prevalence of asthma is increasing steadily among general population in developing countries over past two decades. One of the causative agents of broncho-constriction in asthma is thromboxane A2 receptor (TBXA2R). However few studies of TBXA2R polymorphism were performed so far. The present study aimed to assess potential association of TBXA2R rs34377097 polymorphism causing missense substitution of Arginine to Leucine (R60L) among 482 patients diagnosed with pollen-induced asthma and 122 control participants from West Bengal, India. Also we performed in-silico analysis of mutated TBXA2R protein (R60L) using homology modeling. Methods: Clinical parameters like Forced expiratory volume in 1 second (FEV1), FEV1/Forced vital capacity (FVC) and Peak expiratory flow rate (PEFR) were assessed using spirometry. Patients' sensitivity was measured by skin prick test (SPT) against 16 pollen allergens. Polymerase chain reaction-based Restriction fragment length polymorphism was done for genotyping. Structural model of wild type and homology model of polymorphic TBXA2R was generated using AlphaFold2 and MODELLER respectively. Electrostatic surface potential was calculated using APBS plugin in PyMol. Results: Genotype frequencies differed significantly between the study groups (P=0.03). There was no significant deviation from Hardy-Weinberg equilibrium in control population (χ2=1.56). Asthmatic patients have significantly higher frequency of rs34377097TT genotype than control subjects (P=0.03). SPT of patients showed maximum sensitivity in A. indica (87.68%) followed by C. nusifera (83.29%) and C. pulcherima (74.94%). Significant difference existed for pollen sensitivity in adolescent and young adult (P=0.01) and between young and old adult (P=0.0003). Significant negative correlation was found between FEV1/FVC ratio and intensity of SPT reactions (P<0.0001). Significant association of FEV1, FEV1/FVC and PEFR was observed with pollen-induced asthma. Furthermore, risk allele T was found to be clinically correlated with lower FEV1/FVC ratio (P=0.015) in patients. Our data showed R60L polymorphism, which was conserved across mammals, significantly reduced positive electrostatic charge of polymorphic protein in cytoplasmic domain thus altered downstream pathway and induced asthma response. Discussion: The present in-silico study is the first one to report association of TBXA2R rs34377097 polymorphism in an Indian population. It may be used as prognostic marker of clinical response to asthma in West Bengal and possible target of therapeutics in future.

Polymorphism in ADAM33 gene associated with asthmatics in West Bengal, India - An investigation by in-silico analysis.

Introduction: Asthma is one of the common chronic polygenic inflammatory diseases. Genome wide association studies have identified ADAM33 as an asthma candidate gene. The present study investigated possible association of rs2280090 (T1), rs2280091 (T2) and rs3918396 (S1) single nucleotide polymorphisms (SNPs) of ADAM33 with aeroallergen induced asthma in West Bengal population, India. In addition, in-silico analysis was performed to find out changes in protein function. Methods: Forced expiratory volume in 1 second (FEV1)/Forced vital capacity (FVC), peak expiratory flow rate (PEFR) were assessed using spirometry in 1039 participants. Allergic sensitivity of 619 spirometry positive asthma patients was assessed by skin prick test (SPT) against 22 aeroallergens. For genotyping of T1, T2, and S1 SNPs in 540 allergic asthma patient and 420 control subjects, polymerase chain reaction-based restriction fragment length polymorphism was performed. Total Immunoglobulin-E (IgE) level was measured in both patients and controls. ADAM333 haplotype blocks were constructed using Haploview software v.4.2. Structural model of transmembrane and cytoplasmic domains of ADAM33 was generated using RaptorX. Protein-protein interaction was analysed using the STRING server. Results: Highest number of patient sensitivity was observed towards Cocos nusifera (n = 215) and Dermatophagoides farinae (n = 229). Significant difference in sensitivity was observed between child and late adult (P = 0.03), child and early adult (P = 0.02), adolescent and late adult (P = 0.02) and adolescent and early adult (P = 0.01). Genotypic frequencies differed significantly between patients and controls (P < 0.05). rs2280090 GG, rs2280091GG and AG genotype, and rs3918396 AA carried significant risk for asthma (P = 0.02, P = 0.008, P = 0.04, P = 0.01 respectively). ADAM33 T1, T2, and S1 polymorphisms were in high Linkage Disequilibrium (D = 0.98). Haplotype consisting of rs2280090G, rs2280091G and rs3918396A alleles were found significantly higher in patient population in comparison with controls (OR = 2.03). IgE level differed significantly among different genotypes for T1, T2, and S1 SNPs analysed in pair (P < 0.0001). FEV1/FVC ratio differed significantly among different genotypes for T1, T2 and S1 SNPs analysed in pair (P < 0.0001). Significant difference of FEV1/FVC was also found between GGA and AAG haplotype (P < 0.0001). In-silico analysis revealed T1 and T2 polymorphisms are located in cytoplasmic domain of ADAM33 may cause bronchial smooth muscle cell mobility and cellular hyperplasia as well as cytoskeletal remodelling by altered interaction with different cytoplasmic proteins found by string analysis. Conclusion: Present study showed significant association of T1, T2, and S1 polymorphisms of ADAM33 with aeroallergen-induced asthma in West Bengal, India. These polymorphisms may be used as prognostic markers and possible targets for therapeutics in future.