Prevalence of filaggrin gene polymorphisms (exon-3) in patients with atopic dermatitis in a multiracial Brazilian population.
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ABSTRACT:
SUBMITTER: Laczynski CMM
PROVIDER: S-EPMC9984714 | biostudies-literature | 2023 Mar-Apr
REPOSITORIES: biostudies-literature
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Prevalence of filaggrin gene polymorphisms (exon-3) in patients with atopic dermatitis in a multiracial Brazilian population.
Laczynski Cristina Marta Maria CMM Machado Filho Carlos D'Apparecida Santos CDS Miot Hélio Amante HA Christofolini Denise Maria DM Rodart Itatiana Ferreira IF Criado Paulo Ricardo PR
Anais brasileiros de dermatologia 20230118 2
Similar Datasets
Project description:BACKGROUND:Polymorphisms of the filaggrin 2 gene (rs 12568784 and rs 16899374) are associated with persistent atopic dermatitis in African American patients. Filaggrin 2 is a protein with a function similar to filaggrin and also encoded in the epidermal differentiation complex on chromosome 1q21. OBJECTIVE:To evaluate the polymorphisms in the filaggrin 2 gene (rs 12568784 and rs 16899374) in children and adults with atopic dermatitis and to verify the association of these with the severity of the clinical picture, presence of other allergic diseases, and socio-demographic factors. METHOD:The study was carried out with patients and control group. Questionnaires were used to evaluate ethnicity, sex, age, family history, scoring, atopic dermatitis (SCORAD), among other parameters. Genotyping of the filaggrin 2 gene was performed by real-time polymerase chain reaction. RESULTS:Forty-eight patients and 83 controls were evaluated. No correlation was found between the variables studied in patients with atopic dermatitis and polymorphisms, no significant difference between the prevalence of polymorphisms in the patients and in the control group p>0.05. STUDY LIMITS:The exclusive use of self-reported ethnicity information and the sample size. RESULTS:The results of this work can be an incentive for the study of the polymorphisms in atopic dermaititis, considering the characteristic of the Brazilian multi ethnic population. CONCLUSION:This is an unpublished work in Brazil and the first study in the world to have a control group to evaluate alterations in the gene of filaggrin 2.
| S-EPMC7175100 | biostudies-literature
Project description:Background and purposeThis study aimed to analyze the gender-specific association of the filaggrin (FLG) gene polymorphisms with atopic dermatitis (AD) in Caucasians from the central region of Russia.MethodsThe study sample consisted of 906 female (including 474 patients with AD and 432 controls) and 406 male (such as 226 patients with AD and 180 controls) participants. Genotyping of ten polymorphisms of the FLG gene was done. The logistic regression was used to analyze the associations. A total of 125 SNPs (seven AD-associated SNPs and 118 proxy SNPs, r2≥0.8) FLG gene were used for the in silico functional annotation analysis in the females.ResultsSignificant associations were identified between seven SNPs of the FLG gene (rs12130219, rs61816761, rs558269137, rs12144049, rs3126085, rs471144, rs6661961) and AD in females: rs12144049 was associated independent individually (for allele C OR = 1.71, 95%Сl 1.19-2.46, рperm = 0.004 and OR = 1.76, 95%Сl 1.18-2.63, рperm = 0.006 according to the additive and dominant genetic models, respectively) and seven SNPs of the FLG gene within 14 haplotypes. Haplotype GGT [rs61816761-rs3126085-rs12144049] showed the strongest association (OR = 0.55, рperm = 0.001). No association between the analyzed SNPs and AD was determined in the male group. The subsequent bioinformatic analysis predicted the SNPs of the FLG gene that possessed epigenetic and non-synonymous effects, were involved in the control of gene expression and alternative splicing of genes that contribute to AD pathophysiology.ConclusionPolymorphisms of the FLG gene are associated with AD in females but not in males in the Caucasian population of Central Russia.
| S-EPMC8659355 | biostudies-literature
Project description:Background & objectivesAtopic diseases, including atopic dermatitis (AD), allergy and asthma, are complex diseases resulting from the effect of multiple genetic and interacting environmental factors on their pathophysiology. The genetic basis is incompletely understood; however, recent studies have shown an association between loss-of-function variants of the filaggrin gene (FLG) and atopic dermatitis. The aim of this study was to determine whether FLG variants can serve as a predictor for atopic diseases in Korean individuals.MethodsA total of 648 subjects were genotyped for the FLG P478S (rs11584340, C/T base change) polymorphism (322 patients and 326 controls). Serum levels of free fatty acids (FFA) and IgE were later stratified to determine the effects of the FLG polymorphism on AD.ResultsA significant difference in genotype frequency was found between AD patients and controls in the FLG P478S polymorphism. The FLG P478S T allele carrier (TT+TC) was associated with AD risk (odds ratio = 1.877, 95% confidence interval 1.089 to 3.234). In addition, the P478S T allele was related to high levels of FFA in AD patients (471.79 ± 298.96 vs. 333.54 ± 175.82 μg eq/l, P <0.05).Interpretation & conclusionsThe results of the present study suggest that the FLG P478S polymorphism alone and combined with other factors influences FFA levels and increases the susceptibility to AD.
| S-EPMC3978983 | biostudies-literature
Project description:Data on the allele, genotype and haplotype frequencies of four single nucleotide polymorphisms (SNPs) (rs3126085, rs12144049, rs471144 and rs4363385) filaggrin (FLG) gene in Russian patients with atopic dermatitis are presented. Genome-wide association studies identified these SNPs could be significant genetic markers associated with atopic dermatitis. The frequencies of alleles, genotypes and haplotypes of four SNPs were calculated in 3 groups: entire sample, females and males. No significant differences in the allele, genotype and haplotype frequencies between males and females with AD patients were observed.
| S-EPMC7047013 | biostudies-literature
Project description:Research of the FLG mutation in various ethnic groups revealed non-overlapping mutation patterns. In addition, Japanese and Chinese atopic patients showed somewhat different mutations. These ethnic differences make the research on Korean patients mandatory; however, no systematic research on Korean atopic dermatitis (AD) patients has been performed. This study aims to investigate the genetic polymorphism of FLG in Korean atopic dermatitis patients. The study was made up of three groups including 9 Ichthyosis vulgaris (IV) patients, 50 AD patients and 55 normal controls: the ichthyosis group was incorporated due to the reported association between the FLG mutation and IV. In comparison to other sequencing methods, the overlapping long-range PCR was used. We revealed the genetic polymorphism of filaggrin in Koreans, and at the same time, we discovered nonsense mutations in p.Y1767X and p.K4022X in Korean AD patients. By using FLG sequencing techniques confirmed in this study, new mutations or genetic polymorphisms with ethnic characteristics would be detected and further larger studies of repeat number polymorphisms could be performed.
| S-EPMC4901008 | biostudies-literature
Project description:PurposeAtopic dermatitis (AD) is a chronic, relapsing eczematous inflammatory skin disease. Mutations in the filaggrin gene (FLG) are major predisposing factors for AD. Ethnic differences exist between Asian and European populations in the frequency and spectrum of FLG mutations. Moreover, a distinct set of FLG mutations has been reported in Asian populations. The aim of this study was to examine the spectrum of FLG mutations in Koreans with AD. We also investigated the association of FLG mutations and clinical features of AD and compared the Korean FLG landscape with that of other East Asian countries.Materials and methodsSeventy Korean patients with AD were enrolled in this study. Fourteen FLG mutations previously detected in Korean, Japanese, and Chinese patients were screened by genotyping.ResultsFour FLG null mutations (3321delA, K4022X, S3296X, and S2889X) were identified in eleven patients (15.7%). The most commonly detected mutations in Korean patients with AD were 3321delA (n=6, 9.1%) and K4022X (n=3, 4.5%). FLG mutations were significantly associated with elevated IgE (≥200 KIU/L and/or MAST-CLA >3+, p=0.005), palmar hyperlinearity (p<0.001), and a family history of allergic disease (p=0.021).ConclusionThis study expanded our understanding of the landscape of FLG mutations in Koreans and revealed an association between FLG mutations and AD phenotype.
| S-EPMC5290020 | biostudies-literature
Project description: Not available
| S-EPMC4910377 | biostudies-literature
Project description:BackgroundWhile numerous genetic loci associated with atopic dermatitis (AD) have been discovered, to date, work leveraging the combined burden of AD risk variants across the genome to predict disease risk has been limited.ObjectivesThis study aims to determine whether polygenic risk scores (PRSs) relying on genetic determinants for AD provide useful predictions for disease occurrence and severity. It also explicitly tests the value of including genome-wide association studies of related allergic phenotypes and known FLG loss-of-function (LOF) variants.MethodsAD PRSs were constructed for 1619 European American individuals from the Atopic Dermatitis Research Network using an AD training dataset and an atopic training dataset including AD, childhood onset asthma, and general allergy. Additionally, whole genome sequencing data were used to explore genetic scoring specific to FLG LOF mutations.ResultsGenetic scores derived from the AD-only genome-wide association studies were predictive of AD cases (PRSAD: odds ratio [OR], 1.70; 95% CI, 1.49-1.93). Accuracy was first improved when PRSs were built off the larger atopy genome-wide association studies (PRSAD+: OR, 2.16; 95% CI, 1.89-2.47) and further improved when including FLG LOF mutations (PRSAD++: OR, 3.23; 95% CI, 2.57-4.07). Importantly, while all 3 PRSs correlated with AD severity, the best prediction was from PRSAD++, which distinguished individuals with severe AD from control subjects with OR of 3.86 (95% CI, 2.77-5.36).ConclusionsThis study demonstrates how PRSs for AD that include genetic determinants across atopic phenotypes and FLG LOF variants may be a promising tool for identifying individuals at high risk for developing disease and specifically severe disease.
| S-EPMC8973457 | biostudies-literature
Project description:BackgroundWe confirmed that the filaggrin gene mutation c.3321delA is associated with atopic dermatitis in our previous genome wide association study of the Chinese Han population. c.3321delA is the most common filaggrin gene mutation in Chinese atopic dermatitis patients but is not present in European populations.ObjectiveTo investigate the genetic model for the c.3321delA mutation and to determine the correlation between c.3321delA and atopic dermatitis clinical phenotypes in the Chinese Han population.MethodThe filaggrin gene mutation c.3321delA was sequenced in 1,080 atopic dermatitis patients and 908 controls from the Chinese population. The χ2 test, ANOVA,nonparametric tests and logistic regression were used to investigate the relationship between the c.3321delA genotype and atopic dermatitis clinical phenotypes in the Chinese Han population.ResultsAnalyses of the genetic model revealed that the additive model best described the c.3321delA mutation (P = 3.09E-11, OR = 3.43, 95%CI = 2.38-4.96). Stratified analyses showed that the c.3321delA allele frequency distribution is significantly associated with concomitant skin xerosis (P = 1.68E-03, OR = 2.13,95%CI = 1.32-3.46), palmar hyperlinearity (P = 3.64E-17, OR = 4.0,95%CI = 2.86-5.70), white dermatographism (P = 4.25E-03, OR = 1.82,95%CI = 1.22-2.71), food intolerance (P = 1.51E-03, OR = 1.76,95%CI = 1.23-2.50) and disease severity ( P = 9.67E-05).ConclusionOur study indicates that the filaggrin gene mutation c.3321delA is associated with clinical phenotypes of atopic dermatitis in the Chinese Han population, which might help us gain a better understanding on the pathogenesis of atopic dermatitis.
| S-EPMC4032331 | biostudies-literature
Project description:Atopic dermatitis (AD) is a chronic, relapsing, and inflammatory skin disorder. It is characterized by an inappropriate skin barrier function, allergen sensitization, and recurrent skin infections. Resistin is an adipokine expressed mainly in macrophages and monocytes; it has a role in the inflammatory process and is associated with multiple inflammatory human diseases; however, only few studies linked resistin to atopic dermatitis. This study tested the association between G>A (rs3745367) and C>T (rs3219177) single nucleotide polymorphisms (SNPs) of the RETN gene with atopic dermatitis. In addition, it explored the relationship between serum resistin protein and atopic dermatitis. To achieve objectives of this study, 162 atopic dermatitis patients and 161 healthy participants were recruited in the study. A significant association was detected between rs3745367 and atopic dermatitis with age and gender specificity (p < 0.05), while no significant association between rs3219177 and atopic dermatitis was found (p > 0.05). For the serum resistin levels, a significant decrease was indicated in atopic dermatitis patients compared to healthy subjects (p < 0.05). In conclusion, rs3745367 may play a gender and age-specific role in atopic dermatitis. In addition, the significant decrease in the resistin protein level confirmed this association.
| S-EPMC6023010 | biostudies-literature