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Susanne Stemmler, Qumar Parwez, Elisabeth Petrasch-Parwez, Jörg T. Epplen, Sabine Hoffjan

• \(\bf Background:\) Atopic dermatitis (AD) is a chronic inflammatory skin disorder caused by complex interaction of genetic and environmental factors. Besides mutations in the filaggrin gene, leading to impaired skin barrier function, variation in genes encoding additional skin proteins has been suggested to contribute to disease risk. Laminin 5, playing an important role in skin integrity, is composed of three subunits encoded by the \(\it {LAMA3}\), \(\it {LAMB3}\) and \(\it {LAMC2}\) genes in which biallelic mutations cause epidermolysis bullosa junctionalis. We aimed at evaluating the role of variation in the \(\it {LAMA3}\), \(\it {LAMB3}\) and \(\it {LAMC2}\) genes for AD pathogenesis. \(\bf Methods:\) 29 single nucleotide polymorphisms (SNPs) were genotyped in the three genes in a German AD case-control cohort comprising 470 unrelated AD patients and 320 non-atopic controls by means of restriction enzyme digestion. Allele, genotype and haplotype frequencies were compared between cases and controls using chi-square testing and the Haploview software. \(\bf Results:\) Several SNPs in the \(\it {LAMA3}\) gene showed significant association with AD in our cohort (p<0.01),while we did not detect association with variations in the \(\it {LAMB3}\) and \(\it {LAMC2}\) genes. Haplotype analysis additionally revealed several significantly associated haplotypes in the \(\it {LAMA3}\) gene. Due to extensive linkage disequilibrium, though, we were not able to further differentiate the specific disease causing variation(s) in this region. \(\bf Conclusions:\) We established the \(\it {LAMA3}\) gene as novel potential susceptibility gene for AD. Additional studies in independent cohorts are needed to replicate these results.