A haplotype spanning P2X7R, P2X4R and CAMKK2 may mark susceptibility to pulmonary non-tuberculous mycobacterial disease.
Immunogenetics
; 69(5): 287-293, 2017 05.
Article
en En
| MEDLINE
| ID: mdl-28233049
ABSTRACT
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 < 0.0001; R 2 = 0.05). Examination of individual alleles within these haplotypes implicated P2X7R and CAMKK2 in pathways affecting pulmonary NTM disease.
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Base de datos:
MEDLINE
Asunto principal:
Polimorfismo de Nucleótido Simple
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Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina
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Receptores Purinérgicos P2X4
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Receptores Purinérgicos P2X7
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Enfermedades Pulmonares
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Mycobacterium
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Infecciones por Mycobacterium no Tuberculosas
Tipo de estudio:
Observational_studies
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Risk_factors_studies
Idioma:
En
Revista:
Immunogenetics
Año:
2017
Tipo del documento:
Article