RESUMO
The filaggrin (FLG) gene is one of the most widely replicated susceptibility genes for atopic dermatitis (AD) so far. Yet, FLG mutations cannot fully account for the original linkage peak on chromosome 1q21, a region comprising the so-called epidermal differentiation complex (EDC). Since the EDC contains numerous genes relevant for epidermal differentiation, we sought to evaluate variation in other genes located in this region in a German AD case-control cohort. Thirty-two single nucleotide polymorphisms (SNPs) in 21 genes across the EDC were genotyped in 402 unrelated AD patients and 325 non-atopic controls by means of restriction enzyme digestion or TaqMan assays. Allele and genotype frequencies were tested for differences between patients and controls by logistic regression. Haplotype frequencies were evaluated using the famhap software. Except for the already known association with FLG, we did not identify any additional significant associations of EDC genes with AD. Thus, in this German cohort, there is no evidence that additional genes in the EDC region apart from FLG contribute substantially to AD pathogenesis.
Assuntos
Diferenciação Celular/genética , Dermatite Atópica/genética , Epiderme/imunologia , Frequência do Gene/genética , Proteínas de Filamentos Intermediários/genética , Adolescente , Adulto , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 1/imunologia , Dermatite Atópica/epidemiologia , Epiderme/patologia , Proteínas Filagrinas , Frequência do Gene/imunologia , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Genótipo , Alemanha/epidemiologia , Haplótipos/genética , Haplótipos/imunologia , Humanos , Lactente , Proteínas de Filamentos Intermediários/imunologia , Desequilíbrio de Ligação/genética , Desequilíbrio de Ligação/imunologia , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting up to 16% of children in developed countries. A complex genetic background for AD has been suggested, with genetic as well as environmental factors influencing disease susceptibility. Among other factors, dysregulation in both the innate and the adaptive immune system has been proposed to play a role in AD pathophysiology. We present here an extended association screen for AD using microsatellite markers in 154 genes related to innate and adaptive immunity in pooled DNA samples from 150 German children with AD and 100 controls. After Bonferroni correction, no marker revealed a significant association with AD. Yet, markers representing the nuclear factor kappa B (NFKB)1 and chemokine receptor (CCR)4 genes showed differences in allelic distributions between cases and controls for both pooled DNA analysis and individual genotyping and were thus further investigated. Evaluation of additional single nucleotide polymorphisms (SNP) in the NFKB1 and CCR4 genes revealed no association of individual SNPs with AD. In contrast, haplotype analyses showed a significantly different haplotype distribution between patients and controls for CCR4 (P < 0.001). Furthermore, when SNP-SNP interaction effects were analysed for these two genes, we found significant evidence for epistatic interactions between SNPs within each of the two genes but no evidence for a gene-gene interaction, suggesting that variation in or near both the CCR4 and the NFKB1 genes might individually contribute to AD pathogenesis.