Correction to: Prevalence of Filaggrin Gene R501X Mutation in Indian Children with Allergic Diseases (original) (raw)
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Prevalence of Filaggrin Gene R501X Mutation in Indian Children with Allergic Diseases
The Indian Journal of Pediatrics, 2020
Objective To determine the prevalence of R501X mutation of Filaggrin gene in children with allergic diseases. Methods Ninety patients recruited from Allergy and Asthma clinic of Advanced Pediatric Centre, PGIMER, Chandigarh and 81 healthy controls from local schools matched for age, gender and BMI were enroled in the present study. The R501X mutation analysis was done by PCR-RFLP method. Results Out of the 90 enroled allergic children, 5 (5.5%) were mutant (AA) for R501X genotype, 44 (43.3%) had (AA+Aa) genotype and 46 (51.1%) had (aa) genotype. However, in the control group there were no mutant (AA) for R501X, 36 (44.4%) had (AA+Aa) genotype and 45 had wild type homozygous (aa) genotype. There were 3.3% and 2.2% children with asthma and asthma concomitantly with eczema having mutant R501X genotype. Conclusions In the present study, the prevalence of Filaggrin mutant genotype (R501X) was detected in approximately 5.5% of children with allergic diseases.
Low frequency of filaggrin null mutations in Croatia and their relation with allergic diseases
International Journal of Immunogenetics, 2012
Filaggrin gene (FLG) null mutations are considered associated with atopic dermatitis. This study was conducted to determine the prevalence of FLG null mutations R501X, 2282del4, R2447X and S3247X in the Croatian population and their role in the occurrence of allergic diseases including atopic dermatitis, allergic rhinitis, asthma and allergic contact dermatitis (ACD). Study enrolled 440 freshmen with defined allergic diseases by means of both present symptoms in International Study of Asthma and Allergies in Childhood questionnaire (relevant respiratory and/or skin symptoms) and markers of allergic sensitization (positive skin prick and/or patch test). FLG null mutations were successfully genotyped in 423 students of which 11 (2.6%) were carriers of FLG null mutation: 1/423 (0.2%) was heterozygous for R501X and 10/423 (2.4%) were heterozygous for 2282del4. No carriers of R2447X and S3247X mutations were identified. In wild-type FLG carriers (412 subjects), atopic dermatitis was present in 45 (11%), allergic rhinitis in 70 (17%) and allergic asthma in 29 (7%) students. Twenty-five of 393 (7%) patch-tested wild-type FLG carriers had ACD. Among 11 FLG null mutation carriers, four had one or more allergic diseases, and five had reported skin symptoms without defined allergic sensitization (positive skin prick test and/or patch test). FLG null mutations were not confirmed as a predictor of analysed allergic diseases, but were confirmed as an independent predictor of skin symptoms (OR 17.19, 95% CI 3.41-86.6, P < 0.001). Our results in general indicate a low frequency of FLG null mutations in the studied Croatian population supporting a theory of a latitude-dependent distribution of FGL null mutations in Europe, with a decreasing northsouth gradient of R501X and 2282del4 mutation frequency. The relation between FLG null mutations and skin disorders was confirmed.
Journal of Clinical Medicine
Atopic dermatitis is frequently associated with the onset of other allergic conditions, such as asthma, rhino-conjunctivitis and food allergy. The etiology of atopic dermatitis is marginally understood in spite of the number of predisposing factors, above all, mutations in the Filaggrin gene (FLG). In this study, the association between loss-of-function variants in the FLG gene and other allergic manifestations, in particular food allergy, was evaluated in an Italian pediatric population affected by atopic dermatitis. The 10 more frequently mutated loci in the FLG gene were genotyped in 238 children affected by atopic dermatitis and tested for association with clinical features of allergic disorders by a multivariate logistic regression model. R501X and 2282del4 were the only two mutations identified; 12.2% of children carry one of these variants, corresponding to an allelic frequency of 6.5%. According to multivariate statistical analysis, loss-of-function variants in the FLG gene ...
Central European Journal of Immunology, 2013
Filaggrin is one of the most important structural proteins in the stratum corneum of the human's epidermis. There are known over forty mutations in the filaggrin gene (FLG) of which the null-type mutations such as R501X and 2282del4, localized in exon 3 of this gene, are the most significant risk factors for the development of allergic diseases. The atopic diseases develop in mucosal surfaces such as the gastrointestinal tract, the respiratory tract and the skin. We focus on research characterizing the filaggrin-deficient epidermis with respect to genetic, immunologic and microbiome abnormalities to show the consequences of these mutations in the development and progression of atopy. A case of a 3-yearold girl with food allergy, atopic dermatitis and Staphylococcus aureus infection, which was found by the presence of R501X mutation in the filaggrin gene. The girl remains under strict medical control and is subjected to integrated therapy of allergic diseases.
Journal of Allergy and Clinical Immunology, 2008
Background: Atopic disease is a major health problem. Mutations in the filaggrin gene (FLG) confer major susceptibility to eczema and related asthma. Objective: We sought to determine the natural history and burden of atopic disease conferred by the 2 most common FLG mutations in a large, population-based birth cohort study. Methods: We analyzed the effect of the most common null alleles (R501X and 2282del4) on several atopic phenotypes in a cohort of approximately 7000 English children born in 1990-1991. Results: FLG null alleles associated strongly with eczema; eczema associated with these mutations presents in early life and is more persistent (hazard ratio for eczema resolution for those with FLG mutations to FLG wild type, 0.67; 95% CI, 0.58-0.77; P 5 5 3 10 28 ). FLG mutations conferred a population asthma risk of 1.80 (95% CI, 1.34-2.41; P 5 .00019); asthma risk was especially high in the context of eczema (odds ratio, 3.16; 95% CI, 2.25-4.43; P 5 1.4 3 10 211 ). Strong associations were identified with sensitization to grass, house dust mite, and cat dander and sensitization to multiple allergens (odds ratio, 2.12; 95% CI, 1.03-4.37; P 5 5.42 3 10 227 ). Conclusion: FLG mutations are strong genetic determinants of eczema, early wheeze, asthma in the context of eczema, and atopic sensitization. They confer risk of a particular trajectory for eczema, with increased duration of disease and greater risk of asthma and multiple allergic sensitizations. FLG alleles help define the risk profile of children with eczema and help define the ''eczema plus early wheeze'' and ''eczema plus asthma'' phenotypes. (J Allergy Clin Immunol 2008;121:872-7.)
PLoS ONE, 2011
Background: FLG null variants of which 2282del4 and R501X are the most frequent in Caucasians are established risk factors for atopic dermatitis (AD) with an effect probably mediated through impairment of epidermal barrier. Among subjects with AD FLG defects are also consistently associated with asthma and allergic rhinitis (AR) but it is less clear to what extent these associations are also present independently from skin disease. The aim of the present study was to evaluate the role of 2282del4 and R501X in predisposing to these allergic phenotypes in a Polish population.
International Archives of Allergy and Immunology, 2014
confidence interval (CI) 1.06-1.80] and rhinitis (RR 1.37, 95% CI 1. 16-1.63). In the delayed-effects models, ' FLG variants plus allergic sensitization' and ' FLG variants plus eczema' increased the risk of subsequent asthma by 4.93-fold (95% CI 3.61-6.71) and 3.33-fold (95% CI 2.45-4.51), respectively, during the first 18 years of life. In contrast, neither eczema nor allergic sensitization in combination with FLG variants increased the risk of later rhinitis. Conclusions: Allergic sensitization and eczema modulated the association between FLG variants and asthma but not rhinitis. Our results imply that the mechanisms and pathways through which FLG variants predispose to an increased risk of asthma and rhinitis may be different.
Filaggrin null mutations and childhood atopic eczema: A population-based case-control study
Journal of Allergy and Clinical Immunology, 2008
Background-Null mutations within the filaggrin gene (FLG) are associated with moderatesevere atopic eczema; their role in the mild-moderate eczema in the general population is unknown. Objective-To investigate the significance of five common FLG null mutations in childhood atopic eczema in an unselected population cohort. Methods-811 English children aged 7-9 years were screened for FLG mutations. Eczema cases were defined by UK diagnostic criteria and skin examination. Asthma and seasonal rhinitis cases were defined by parental questionnaire. Association between phenotype and genotype was investigated using Fisher's exact test and logistic regression analysis. Results-The 12-month period prevalence of atopic eczema was 24.2% (95% confidence interval 21.2-27.2%) with 96% (115/120) of cases having mild-moderate disease. The combined null genotype (carriage of one or more FLG mutations) was significantly associated with atopic eczema (p=1.2x10-4). The odds ratio for individuals carrying two null mutations was 26.9 (95% CI 3.3-217.1), but heterozygote carriers showed no significant increase in risk (odds ratio 1.2, 95% confidence interval 0.7-1.9). 8/190 (4.2%) of eczema cases carried two FLG null mutations and thus may be attributed to filaggrin deficiency. Asthma in the context of eczema showed significant association with the FLG null mutations (p=7.1x10-4 , OR for carriers of two mutant alleles 11.9,
Clinical & Experimental Allergy, 2014
Background-Allergic sensitization and filaggrin gene (FLG) variants are important risk factors for allergic disorders; however, knowledge on their individual and interactive effects on the coexistence of eczema, asthma, and rhinitis is lacking. Objective-This study aimed at investigating the single and combined effects of allergic sensitization and FLG variants on the development of single and multiple allergic disorders. Methods-The Isle of Wight Birth Cohort (n = 1,456) has been examined at 1, 2, 4, 10, and 18 years of age. Repeated measurements of eczema, asthma, rhinitis, and skin prick tests were available for all follow-ups. FLG variants were genotyped in 1,150 participants. Associations of allergic sensitization and FLG variants with single and multiple allergic disorders were tested in log-binomial regression analysis.