Filaggrin Gene Mutation c.3321delA is Associated with Dry Phenotypes of Atopic Dermatitis in the Chinese Han Population.
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ABSTRACT:
SUBMITTER: Zhong WL
PROVIDER: S-EPMC4910377 | biostudies-literature | 2016 Jun
REPOSITORIES: biostudies-literature
Publications
Filaggrin Gene Mutation c.3321delA is Associated with Dry Phenotypes of Atopic Dermatitis in the Chinese Han Population.
Zhong Wei-Long WL Wu Xia X Yu Bo B Zhang Jie J Zhang Wei W Xu Ning N Zhou Jing J Zheng Jie-Cheng JC Chen Xiao-Fan XF Dou Xia X
Chinese medical journal 20160601 12
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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: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:BackgroundStudies investigated the associations between four Vitamin D receptor (VDR) common variations and interactions of gene-environment factors and atopic dermatitis (AD) in Chinese population are few.MethodsIn this case-control study, 400 AD patients and 400 controls were genotyped for the FokI, TaqI, BsmI and ApalI variations of VDR genes by restriction fragment length polymorphism analysis. The associations between VDR genes and AD were assessed by univariate and multivariate logistic regression. The interactions between VDR genes and some risk factors were also explored using cross-over analysis. The corresponding odds ratio (ORs) and 95% confidence intervals (CI) were also calculated.ResultsThe FoKI rs2228570 polymorphism was significantly associated with an increased risk of atopic dermatitis in the co-dominant model (OR=2.93, 95% CI: 1.78-4.82. P=0.000), recessive model (OR=2.67, 95% CI: 1.68-4.26, P=0.000) and dominant model (OR=1.38, 95% CI: 1.04-1.84, P=0.028), and allele model. No significant associations were found among TaqI, BsmI and ApalI polymorphism and AD. The C-A-T-C and C-G-T-T haplotypes significantly increased the risk of atopic dermatitis. For rs2228570, the increased effects were more evident in the subgroups of age ≤8-month, cow milk and mixed, and keeping pet. Interactions between rs2228570 gene polymorphism and family history, age >8, and keeping pet increased the AD risk. The rs2228570 C allele decreased the relative mRNA expression.ConclusionThe FokI rs2228570 C allele of VDR gene could be a risk candidate gene for AD. Interactions between FokI polymorphism and family history and some behaviors may increase the risk of AD.
| S-EPMC8435479 | 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: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: Not available
| S-EPMC9984714 | 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:BackgroundFilaggrin gene (FLG) mutations have been identified as the cause of ichthyosis vulgaris (IV) and major predisposing factors for atopic dermatitis (AD). The relationship among AD, IV and FLG mutations has not been clarified yet. Mutations 3321delA and K4671X, two of the most common mutations in Chinese patients, were both statistically associated with AD in case-control studies.Materials and methodsA group of 100 family trios (a total of 300 members with one affected AD proband and both parents) were recruited and screened for three filaggrin null mutations (3222del4, 3321delA and K4671X). The subjects' manifestations of AD and IV were assessed by two experienced dermatologists and recorded in detail. The relationship of common mutations to AD were assessed using both case-control and family-based tests of association. Filaggrin expression was measured in skin of 3 subjects with K4671X heterozygote and the normal control using quantitative real-time RT-PCR and immunohistochemistry.ResultsOf 100 probands for AD, 22 were carriers for common FLG mutations and only 2 of them were from 40 none-IV family trios (5.00%), consistent with that of the healthy control group (3.99%, P>0.05). Significant statistical associations were revealed between AD and 3321delA (P<0.001, odds ratio 12.28, 95% confidence interval 3.35-44.98) as well as K4671X (P = 0.002, odds ratio 4.53, 95% confidence interval 1.77-11.60). The family-based approach revealed that 3321delA was over-transmitted to AD offspring from parents (T:U = 12∶1, P = 0.003) but failed to demonstrate transmission disequilibrium between K4671X and AD (T:U = 10∶8, P = 0.815). Moreover, compared to the normal control, filaggrin expression at both mRNA and protein levels in epidermis of subjects with K4671X(heter) was not reduced.ConclusionsAD patients from none-IV family trios have low probability of carrying FLG mutations. The present family samples confirmed the susceptibility of mutation 3321delA to AD in Han Chinese. K4671X was not a pathogenic mutation.
| S-EPMC3496733 | 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:IntroductionAtopic Dermatitis (AD) is a chronic inflammatory skin disease that affects almost 20% of children and 2 -10% of adults worldwide. Previous studies revealed that Interleukin-6 (IL-6) plays an essential role in autoimmune and chronic inflammatory diseases. This study aims to investigate the associations between IL-6 polymorphisms and AD.MethodsBlood samples were collected from 132 AD patients and 100 controls, and single nucleotide polymorphisms (SNPs) in IL-6 (rs2069840 (C/G), rs2066992 (G/T), rs2069837 (A/G) and rs1800796 (G/C)) were analyzed using Multiplex PCR-Based Next Generation Sequencing (NGS).ResultsResults showed that the A/G genotype of IL-6/rs2069837 was significantly associated with a 1.933-fold increased risk of AD compared to those patients with A/A genotype (OR 1.933; 95%CI 1.086-3.438; p=0.024). The combined A/G-G/G genotype raised AD risk by 1.856 times compared to patients with the A/A genotype in dominant model (OR: 1.856; 95% CI: 1.056-3.261; p=0.030). No association was observed for 3 other SNPs and 4 haplotypes.DiscussionThese findings suggested that the A/G genotype of IL-6/rs2069837 was more susceptible to AD than A/A genotype in Chinese Han children, indicating the risk role of IL-6/rs2069837 in the occurrence of AD.
| S-EPMC10070860 | biostudies-literature