A haplotype spanning P2X7R, P2X4R and CAMKK2 may mark susceptibility to pulmonary non-tuberculous mycobacterial disease

Despite widespread exposure to potentially pathogenic mycobacteria present in the soil and in domestic water supplies, it is not clear why only a small proportion of individuals contract pulmonary nontuberculous mycobacterial (NTM) infections. Here, we explore the impact of polymorphisms within thre...

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Bibliographic Details
Published in:Immunogenetics (New York) 2017-05, Vol.69 (5), p.287-293
Main Authors: Halstrom, Samuel, Cherry, Catherine L., Black, Michael, Thomson, Rachel, Goullee, Hayley, Baltic, Svetlana, Allcock, Richard, Temple, Suzanna E L, Price, Patricia
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Allergology
Biomedical and Life Sciences
Biomedicine
Calcium-Calmodulin-Dependent Protein Kinase Kinase - genetics
Case-Control Studies
Cell Biology
Disease
Female
Gene Function
Genes
Genetic Predisposition to Disease
Genomics
Haplotypes
Health care
Human Genetics
Humans
Immunology
Kinases
Ligands
Lung Diseases - epidemiology
Lung Diseases - genetics
Lung Diseases - microbiology
Male
Medical research
Middle Aged
Mycobacterium
Mycobacterium - pathogenicity
Mycobacterium Infections, Nontuberculous - epidemiology
Mycobacterium Infections, Nontuberculous - genetics
Mycobacterium Infections, Nontuberculous - microbiology
Original Article
Polymorphism
Polymorphism, Single Nucleotide
Proteins
Receptors, Purinergic P2X4 - genetics
Receptors, Purinergic P2X7 - genetics
Tuberculosis
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Summary:Despite widespread exposure to potentially pathogenic mycobacteria present in the soil and in domestic water supplies, it is not clear why only a small proportion of individuals contract pulmonary nontuberculous mycobacterial (NTM) infections. Here, we explore the impact of polymorphisms within three genes: P2X ligand gated ion channel 7 ( P2X7R ), P2X ligand gated ion channel 4 ( P2X4R ) and calcium/calmodulin-dependent protein kinase kinase 2 beta ( CAMKK2 ) on susceptibility. Thirty single nucleotide polymorphisms (SNPs) were genotyped in NTM patients ( n  = 124) and healthy controls ( n  = 229). Weak associations were found between individual alleles in P2X7R and disease but were not significant in multivariate analyses adjusted to account for gender. Haplotypes spanning the three genes were derived using the fastPHASE algorithm. This yielded 27 haplotypes with frequencies >1% and accounting for 63.3% of the combined cohort. In univariate analyses, seven of these haplotypes displayed associations with NTM disease above our preliminary cut-off ( p  ≤ 0.20). When these were carried forward in a logistic regression model, gender and one haplotype (SH95) were independently associated with the disease (model p  
ISSN:0093-7711
1432-1211
DOI:10.1007/s00251-017-0972-z