title: Genetics of rhinosinusitis.
abstract: Suggestion for a potential genetic basis to chronic rhinosinusitis (CRS) is afforded by degree of inheritability suggested from family and twin studies, existence of CRS in simple mendelian diseases, and development of sinusitis as part of the phenotype of certain gene "knockout" murine models. Genetic association studies are expected to identify novel genes associated with CRS and suggest novel mechanisms implicated in disease development. Although these studies are subject to methodologic difficulties, associations of CRS and polymorphisms in more than 30 genes have been published, with single nucleotide polymorphisms in 3 (IL1A, TNFA, AOAH) replicated. While the individual risk conferred by these single nucleotide polymorphisms remains modest, taken as a group, they suggest an important implication of pathways of innate immune recognition and in regulation of downstream signaling in the development of CRS. In a demonstration of these techniques' potential to identify new targets for research, the authors present a functional investigation of LAMB1, the top-rated gene from a pooling-based genome-wide association study of CRS. Upregulation of gene expression in LAMB1 and associated laminin genes in primary epithelial cells from CRS patients implicates the extracellular matrix in development of CRS and offers a new avenue for further study.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Centre de Recherche du CHUM (CRCHUM), Hôpital Hôtel-Dieu, Université de Montréal, QC, Canada.
authors.forename: Leandra
authors.initials: L
authors.lastname: Mfuna-Endam
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Martin Y
authors.initials: MY
authors.lastname: Desrosiers
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D055106:Genome-Wide Association Study; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D053582:Interleukin-1alpha / Q000235:genetics / Q000276:immunology; D007797:Laminin / Q000235:genetics* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020641:Polymorphism, Single Nucleotide; D012220:Rhinitis / Q000235:genetics* / Q000276:immunology; D012852:Sinusitis / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: C508584:IL1A protein, human; D053582:Interleukin-1alpha; C478221:LAMB1 protein, human; D007797:Laminin; D014409:Tumor Necrosis Factor-alpha