title: HLA and asthma phenotypes/endotypes: a review.
abstract: Asthma is a complex chronic inflammatory disease of the airways caused by the interaction of genetic susceptibility with environmental influences. Genome-wide association studies (GWAS) represent the most powerful approach for asthma, that have identified several genes (e.g., IL18R1, IL33, SMAD3, ORMDL3, HLA-DQ and IL2RB loci). HLA super-locus is a genomic region in the chromosomal position 6p21. Since no gene can be considered as an asthma gene, able to reflect the complex etiology and the heterogeneity of the disease the terms 'phenotype' and more recently 'endotype' have been used. This review, according to literature availability, focuses on the relationship between human leukocyte antigens (HLA) region specifically the HLA class II genes and different asthma phenotypes/endotypes, such as allergic asthma/Th2 associated, occupational and aspirin-sensitive asthma. The most common HLA haplotypes in the different asthma phenotypes are HLA-DRB1in allergic asthma, HLA-DQB1in occupational asthma and HLA-DPB1 in aspirin-sensitive asthma. However, it is difficult to study the role of class II genes in vivo because of the heterogeneity of human population, the complexity of MHC, and the strong linkage disequilibrium among different class II genes. Despite the variation and the inconsistency of the HLA haplotypes and alleles in different types of asthma, the association between HLA class II genes and asthma has been demonstrated in the majority of studies.
authors.affiliation: Asthma Clinic, Pulmonary Department, Aristotle University of Thessaloniki, George Papanikolaou Hospital, Exochi, Thessaloniki, Greece.
authors.forename: Eirini
authors.initials: E
authors.lastname: Kontakioti
authors.affiliation: Asthma Clinic, Pulmonary Department, Aristotle University of Thessaloniki, George Papanikolaou Hospital, Exochi, Thessaloniki, Greece.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Domvri
authors.affiliation: Asthma Clinic, Pulmonary Department, Aristotle University of Thessaloniki, George Papanikolaou Hospital, Exochi, Thessaloniki, Greece. Electronic address: dpapakos@med.auth.gr.
authors.forename: Despina
authors.initials: D
authors.lastname: Papakosta
authors.affiliation: Immunology Research Laboratory, 1st Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece.
authors.forename: Michail
authors.initials: M
authors.lastname: Daniilidis
mesh_terms: D055963:Asthma, Aspirin-Induced / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D059366:Asthma, Occupational / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D002896:Chromosomes, Human, Pair 6; D005786:Gene Expression Regulation / Q000276:immunology*; D018740:Genetic Heterogeneity; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D015810:Linkage Disequilibrium; D010641:Phenotype
chemical_list: D000949:Histocompatibility Antigens Class II
keywords: Allergic; Aspirin; Asthma; HLA; Occupational