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Immunogenetics

, Volume 69, Issue 5, pp 287–293 | Cite as

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

  • Samuel Halstrom
  • Catherine L. Cherry
  • Michael Black
  • Rachel Thomson
  • Hayley Goullee
  • Svetlana Baltic
  • Richard Allcock
  • Suzanna E L Temple
  • Patricia Price
Original Article

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.

Keywords

Non-tuberculous mycobacteria Genetic polymorphism Pulmonary disease Immunogenetics 

Notes

Acknowledgements

Samuel Halstrom was supported by the Gallipoli Medical Research Foundation Research Scholarship during the course of this study.

Funding support was provided through an Academic Title Holder Grant from the University of QLD and Gallipoli Medical Research Foundation, held by Rachel Thomson.

The authors gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program received by the Burnet Institute (CLC).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Samuel Halstrom
    • 1
    • 2
    • 3
  • Catherine L. Cherry
    • 4
    • 5
  • Michael Black
    • 6
  • Rachel Thomson
    • 1
    • 3
  • Hayley Goullee
    • 7
  • Svetlana Baltic
    • 8
  • Richard Allcock
    • 9
    • 10
  • Suzanna E L Temple
    • 8
  • Patricia Price
    • 2
    • 5
  1. 1.School of Medicine and Biomedical ScienceUniversity of QueenslandBrisbaneAustralia
  2. 2.School of Biomedical ScienceCurtin UniversityPerthAustralia
  3. 3.Gallipoli Medical Research FoundationGreenslopes Private HospitalBrisbaneAustralia
  4. 4.Centre for Biomedical Research, Burnet Institute, and Department of Infectious DiseasesAlfred Hospital and Monash UniversityMelbourneAustralia
  5. 5.School of PhysiologyUniversity of the WitwatersrandJohannesburgSouth Africa
  6. 6.Centre for Comparative GenomicsMurdoch UniversityPerthAustralia
  7. 7.Harry Perkins Institute of Medical ResearchPerthAustralia
  8. 8.Institute for Respiratory HealthUniversity of Western AustraliaNedlandsAustralia
  9. 9.Translational Cancer Pathology LaboratoryPathWest Laboratory Medicine W.ANedlandsAustralia
  10. 10.School of Pathology and Laboratory MedicineUniversity of Western AustraliaNedlandsAustralia

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