title: Association of variation in the LAMA3 gene, encoding the alpha-chain of laminin 5, with atopic dermatitis in a German case-control cohort.
abstract: 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 LAMA3, LAMB3 and LAMC2 genes in which biallelic mutations cause epidermolysis bullosa junctionalis. We aimed at evaluating the role of variation in the LAMA3, LAMB3 and LAMC2 genes for AD pathogenesis.
  
  
  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.
  
  
  RESULTS
  Several SNPs in the LAMA3 gene showed significant association with AD in our cohort (p <0.01), while we did not detect association with variations in the LAMB3 and LAMC2 genes. Haplotype analysis additionally revealed several significantly associated haplotypes in the LAMA3 gene. Due to extensive linkage disequilibrium, though, we were not able to further differentiate the specific disease causing variation(s) in this region.
  
  
  CONCLUSIONS
  We established the LAMA3 gene as novel potential susceptibility gene for AD. Additional studies in independent cohorts are needed to replicate these results.
authors.forename: Susanne
authors.initials: S
authors.lastname: Stemmler
authors.forename: Qumar
authors.initials: Q
authors.lastname: Parwez
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Petrasch-Parwez
authors.forename: Joerg T
authors.initials: JT
authors.lastname: Epplen
authors.affiliation: Department of Human Genetics, Ruhr-University, Universitätsstrasse 150, 44801 Bochum, Germany. sabine.hoffjan@rub.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hoffjan
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000235:genetics*; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007797:Laminin / Q000235:genetics*; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D000091344:Filaggrin Proteins; D007797:Laminin; D000097794:Kalinin; C000717249:FLG protein, human; C400567:LAMC2 protein, human; C095567:laminin alpha 3