engleski

Relation of filaggrin null mutations with atopy in Croatia

Background: Null mutations in the gene encoding filaggrin (FLG), which result in the loss of filaggrin production and hence disrupt the epidermal barrier function, have been strongly associated with atopic dermatitis and present a predisposing factor in the development of the atopic march. The frequencies of the most common null mutations among the Caucasian population in Western Europe and North America were analyzed in young adult Croatian population, and their relation to skin and respiratory atopic diseases was assessed. Method: FLG null mutations R501X, 2282del4, R2447X and S3247X were genotyped in 423 students (305 females and 118 males, median age 19 years) with defined atopic phenotype (atopic dermatitis, rhinitis and asthma) by means of recorded atopic skin and respiratory symptoms with modified ISAAC questionnaire and positive skin prick testing (SPT) to one or more common inhalatory allergens. Result: We found 11 FLG null mutations carriers, 1/423 (0.2%) heterozygous for R501X and 10/423 (2, 4%) heterozygous for 2282del4. There were no carriers of R2447X and S3247X mutations. In total sample (N=423), atopic dermatitis was present in 12%, rhinitis in 17% and asthma in 7% of subjects. FLG null mutations were not related to any analyzed atopic phenotype. Among 11 FLG null mutations carriers only 3 (27.3%) had atopic dermatitis, but 9 had eczema/dermatitis symptoms regardless of positive SPT. Multiple logistic regression analysis, controlled for gender, family history of skin allergies and positive SPT, confirmed FLG null mutations as an independent risk factor for presence of eczema/dermatitis symptoms (OR 22, 95%CI 4.4-109.4 ; P<0.0001). Conclusion: The frequency of FLG null mutation 2282del4 in tested Croatian population was similar to frequency established in other European studies on Caucasian populations (2-5%). Prevalence of other tested null mutations was below 1% in our sample, differing from other studies mainly for R501X. FLG null mutation 2282del4 was strongly associated with a more frequent expression of eczema/dermatitis symptoms, but not with any analyzed atopic phenotype. The majority of subjects with atopic dermatitis, rhinitis or asthma were wild type FLG carriers. This indicates that other genetic and/or environmental factors, rather than the tested FLG null mutations should be investigated for contribution to the development of atopic diseases in Croatian population.

eczema/dermatitis; filaggrin; gene polymorphism; skin prick testing

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