Human leukocyte antigen-G 3’ untranslated region polymorphisms are associated with asthma severity

Human leukocyte antigen-G 3’ untranslated region polymorphisms are associated with asthma severity

•Asthma presents differential inflammatory responses according to disease severity.•HLA-G inhibits the function of the innate and adaptive immune responses.•A gene region close to HLA-G has been independently associated with asthma.•HLA-G 3’UTR polymorphisms are associated with HLA-G production.•Two...

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Bibliographic Details
Published in:Molecular immunology Vol. 101; pp. 500 - 506
Main Authors: Alves, Cinthia C., Arruda, Luísa K.P., Oliveira, Fabíola R., Massaro, Juliana D., Aquino, Beatriz J., Paz, Michelle A., Castelli, Erick C., Mendes-Junior, Celso T., Donadi, Eduardo A.
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01-09-2018
Subjects:
3' Untranslated Regions - genetics
Adolescent
Adult
Aged
Aged, 80 and over
Asthma
Asthma - genetics
Asthma - pathology
Child
Female
Gene Frequency - genetics
Genetic Predisposition to Disease
Haplotypes - genetics
HLA-G
HLA-G Antigens - genetics
Humans
Linkage Disequilibrium - genetics
Male
MHC
Middle Aged
Mild asthma
Polymorphism, Single Nucleotide - genetics
Severe asthma
Severity of Illness Index
Susceptibility
Young Adult
MHC
Mild asthma
Severe asthma
Susceptibility
HLA-G
Asthma
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Summary:•Asthma presents differential inflammatory responses according to disease severity.•HLA-G inhibits the function of the innate and adaptive immune responses.•A gene region close to HLA-G has been independently associated with asthma.•HLA-G 3’UTR polymorphisms are associated with HLA-G production.•Two HLA-G gene variation sites were differentially associated with asthma severity. Asthma is a genetically complex chronic inflammatory airway disorder, and according to disease pathogenesis, clinical manifestations may vary according to asthma severity. A gene region close to the human leukocyte antigen-G (HLA-G) gene was identified as an independent susceptibility marker for asthma. Considering that the HLA-G immune checkpoint molecule may modulate inflammation, we evaluated the diversity of the HLA-G 3′ untranslated region (3′UTR) in asthmatic patients stratified according to disease severity. We evaluate the entire HLA-G 3′UTR segment in 115 Brazilian patients stratified into mild (n=29), moderate (n=21) and severe asthmatics (n=65), and in 116 healthy individuals. HLA-G 3′UTR typing was performed using Sanger sequencing. The multiple comparisons among patients stratified according to disease severity revealed several associations; however, after Bonferroni’s correction, the following results remained significant: i) the +3010C and +3142G alleles were overrepresented in mild asthma patients when compared to controls; ii) the +3010G and +3142C alleles were overrepresented in severe asthma patients in comparison to patients with mild asthma. In conclusion, the +3010C/G and +3142C/G HLA-G 3′UTR variation sites were differentially associated according to asthma severity.
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ISSN:0161-5890
1872-9142
DOI:10.1016/j.molimm.2018.08.013