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Background: A genotype study of filaggrin gene loss-of-function mutations in central India can provide valuable insights into the prevalence and association of these mutations with atopic dermatitis (AD) and ichthyosis vulgaris (IV) in the region. The FLG R501X and 2282del4 are both genetic variants in the human gene called filaggrin gene (FLG), which encodes a protein that plays an important role in the formation and maintenance of the skin barrier. In this study, we determined the FLG R501X and 2282del4 variants association with both AD and IV in Central Indian populations. Materials and Methods: This case--control study was conducted in the Departments of Dermatology and Molecular and Virology Research and Diagnostic Laboratory at Sri Aurobindo Medical College and Post Graduate Institute, Indore (Madhya Pradesh). The study was approved by the Clinical Research and Ethics Committee. A total of 180 patients aged between 3 months - 60 years who attended the skin outpatient department between March-2021 to June-2022 were recruited in this study. Among them, 60 patients were in AD-group, 60 patients in IV-group, and 60 patients were in the healthy control group. Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) was used in genotyping for FLG mutations (R501X and 2282del4). Results: The most common FLG mutations were R501X (31.6% and 23.3%) and 2282del4 (18.3% and 13.3%) in AD and IV patients with heterozygous (AT) genotype, respectively. The combined mutation (FLG R501X and 2282del4) association was 10% and 5% in the AD and IV groups with heterozygous (AT) genotype, respectively, and in all the patients of control group with wild genotype (AA). There were no significant (P = 0.09) associations found with 2282del14 genotype. Conclusion: The R501X mutation in the gene encoding filaggrin is one of the robust genetic associations of AD and IV. The 2282del4 polymorphism was marginally less as compared to R501X. [ABSTRACT FROM AUTHOR]

Background: Atopic Dermatitis (AD) has been associated with the loss of function (LoF) mutations in Filaggrin (FLG) gene and increase in relative abundance of specific microbes in the lesional skin, predominantly in Caucasians. Our study aims to determine, in Indian AD patients, (a) the prevalence of FLG LoF and missense mutations, and (b) the nature and extent of dysbiosis and altered microbial pathways with and without mutations in FLG. AD patients (n = 34) and healthy controls (n = 54) were recruited from India in this study and shotgun sequencing was carried out in a subset of samples with adequate microbiome DNA concentration. Host DNA from the same subset of samples was subjected to FLG coding region sequencing and host-microbiome association was estimated. Results: The prevalence of FLG LoFs that are associated with AD globally were significantly lesser in our cases and controls (8.6%, 0%) than those reported in Europeans (27%, 2.6%). Staphylococcus aureus was present only on AD skin [abundance in Pediatric AD: 32.86%; Adult AD: 22.17%], but not on healthy skin on which Staphylococcus hominis (Adult controls: 16.43%, Adult AD: 0.20%; p = 0.002), Cutibacterium acne s (Adult controls:10.84%, Adult AD: 0.90%; p = 0.02), and Malassezia globosa (Adult controls: 8.89%, Adult AD: 0.005%; p = 0.001) were significantly more abundant. Microbial pathways mostly associated with skin barrier permeability, ammonia production and inflammation (Arginine and Proline metabolism, Histidine Metabolism and Staphylococcus aureus infection) were significantly enriched on AD skin metagenome. These pathways are also reported to impair antimicrobial peptide activity. Among AD patients with missense single nucleotide polymorphisms harboring "potentially damaging" alleles in FLG gene, damaging allele dosage was significantly (p < 0.02) positively correlated with relative abundance of phylum_Proteobacteria up to order_ Pseudomonadales and negatively correlated with phylum_ Firmicutes up to species_ Staphylococcus aureus. Conclusion: Our study has provided evidence that host DNA profile is significantly associated with microbiome composition in the development of AD. Species and strain level analysis showed that the microbial pathways enriched in AD cases were mostly found in MRSA strains. These evidences can be harnessed to control AD by modulating the microbiome using a personalized strategy. Our findings on the association of FLG genotypes with the microbiome dysbiosis may pave the way for a personalized strategy to provide a more effective control of AD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]