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Filaggrin gene mutations and new SNPs in asthmatic patients: a cross-sectional study in a Spanish population.

ABSTRACT: BACKGROUND:Several null-mutations in the FLG gene that produce a decrease or absence of filaggrin in the skin and predispose to atopic dermatitis and ichthyosis vulgaris have been described. The relationship with asthma is less clear and may be due to the influence of atopy in patients with associated asthma. METHODS:Four hundred individuals were included, 300 patients diagnosed with asthma divided into two groups according to their phenotype (allergic and non-allergic asthma) and 100 strictly characterized controls. The coding region and flanking regions of the FLG gene were amplified by PCR. We proceeded to the characterization of potential gene variants in that region by RFLP and sequencing and analysed their association with lung function parameters, asthma control and severity, and quality of life. RESULTS:We identified two null-mutations (R501X and 2282del4), seven SNPs previously described in databases and three SNPs that had not been previously described. One of the SNP identified in this study (1741A > T) was more frequently detected in patients with non-allergic asthma, worse FVC, FEV1 and PEF values and a higher treatment step. In addition, lowered spirometric values were observed in the non-allergic group carrying any of the nonsynonymous SNPs. CONCLUSIONS:In the association study of genetic variants of the FLG gene in our population the 1741A > T polymorphism seems to be associated with non-allergic asthma.

SUBMITTER: Cubero JL

PROVIDER: S-EPMC4960762 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Filaggrin gene mutations and new SNPs in asthmatic patients: a cross-sectional study in a Spanish population.

Cubero José Luis JL Isidoro-García María M Segura Nieves N Benito Pescador David D Sanz Catalina C Lorente Félix F Dávila Ignacio I Colás Carlos C

Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 20160726

<h4>Background</h4>Several null-mutations in the FLG gene that produce a decrease or absence of filaggrin in the skin and predispose to atopic dermatitis and ichthyosis vulgaris have been described. The relationship with asthma is less clear and may be due to the influence of atopy in patients with associated asthma.<h4>Methods</h4>Four hundred individuals were included, 300 patients diagnosed with asthma divided into two groups according to their phenotype (allergic and non-allergic asthma) and ...[more]

PMID: 27462351

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Project description:BackgroundAn increase in chronic conditions is currently the greatest threat to human health and to the sustainability of health systems. Risk adjustment systems may enable population stratification programmes to be developed and become instrumental in implementing new models of care.The objectives of this study are to evaluate the capability of ACG-PM, DCG-HCC and CRG-based models to predict healthcare costs and identify patients that will be high consumers and to analyse changes to predictive capacity when socio-economic variables are added.MethodsThis cross-sectional study used data of all Basque Country citizens over 14 years of age (n = 1,964,337) collected in a period of 2 years. Data from the first 12 months (age, sex, area deprivation index, diagnoses, procedures, prescriptions and previous cost) were used to construct the explanatory variables. The ability of models to predict healthcare costs in the following 12 months was assessed using the coefficient of determination and to identify the patients with highest costs by means of receiver operating characteristic (ROC) curve analysis.ResultsThe coefficients of determination ranged from 0.18 to 0.21 for diagnosis-based models, 0.17-0.18 for prescription-based and 0.21-0.24 for the combination of both. The observed area under the ROC curve was 0.78-0.86 (identifying patients with a cost higher than P-95) and 0.83-0.90 (P-99). The values of the DCG-HCC models are slightly higher and those of the CRG models are lower, although prescription information could not be used in the latter. On adding previous cost data, differences between the three systems decrease appreciably. Inclusion of the deprivation index led to only marginal improvements in explanatory power.ConclusionThe case-mix systems developed in the USA can be useful in a publicly financed healthcare system with universal coverage to identify people at risk of high health resource consumption and whose situation is potentially preventable through proactive interventions.

Project description:ImportanceThe families evaluated in this study represent the second report of cone-rod dystrophy (CRD) cases caused by mutations in RAB28, a recently discovered gene associated with CRD.ObjectiveTo determine the disease-causing gene in 2 families of Spanish descent presenting with CRD who do not have ABCA4 mutations.Design, setting, and participantsMolecular genetics and observational case studies of 2 families, each with 1 affected proband with CRD and 3 or 5 unaffected family members. The affected individual from each family received a complete ophthalmic examination including assessment of refractive errors and best-corrected visual acuity, biomicroscopy, color fundus photography, electroretinography analysis, and visual-evoked potential analysis. After complete sequencing of the ABCA4 gene with negative results, the screening for disease-causing mutations was performed by whole-exome sequencing. Possible disease-associated variants were determined by filtering based on minor allele frequency, predicted pathogenicity, and segregation analysis in all family members.Main outcomes and measuresThe appearance of the macula was evaluated by clinical examination, fundus photography, and fundus autofluorescence imaging, and visual function was assessed by electroretinography. Disease-causing mutations were assessed by sequence analyses.ResultsOphthalmologic findings included markedly reduced visual acuity, bull's eye maculopathy, foveal hyperpigmentation, peripapillary atrophy, dyschromatopsia, extinguished photopic responses, and reduced scotopic responses observed on electroretinography consistent with the CRD phenotype often associated with ABCA4 mutations. Although no ABCA4 mutations were detected in either patient, whole-exome sequencing analysis identified 2 new homozygous mutations in the recently described RAB28 gene, the c.172 + 1G>C splice site variant in IVS2 and the missense c.T651G:p.C217W substitution. Both variants were determined as deleterious by predictive programs and were segregated with the disease in both families. Sequencing of 107 additional patients of Spanish descent with CRD did not reveal other cases with RAB28 mutations.Conclusions and relevanceDeleterious mutations in RAB28 result in a classic CRD phenotype and are an infrequent cause of CRD in the Spanish population.

Dataset Information

Filaggrin gene mutations and new SNPs in asthmatic patients: a cross-sectional study in a Spanish population.

Publications

Filaggrin gene mutations and new SNPs in asthmatic patients: a cross-sectional study in a Spanish population.

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