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Thorax. 2017 Apr;72(4):304-310. doi: 10.1136/thoraxjnl-2016-208775. Epub 2016 Aug 8.

FUT2 genotype influences lung function, exacerbation frequency and airway microbiota in non-CF bronchiectasis.

Author information

1
South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
2
SAHMRI Microbiome Research Laboratory, School of Medicine, Flinders University, Adelaide, South Australia, Australia.
3
Flinders Centre for Epidemiology and Biostatistics, School of Medicine, Flinders University, Adelaide, South Australia, Australia.
4
School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
5
Immunity, Infection, and Inflammation Program, Mater Research Institute, University of Queensland and Translational Research Institute, Woolloongabba, Queensland, Australia.
6
Mater Health Services, South Brisbane, Queensland, Australia.
7
Department of Microbiology and Infectious Diseases, Flinders University, Adelaide, South Australia, Australia.
8
SA Pathology, Flinders Medical Centre, Bedford Park, South Australia, Australia.

Abstract

OBJECTIVE:

To assess whether FUT2 (secretor) genotype affects disease severity and airway infection in patients with non-cystic fibrosis bronchiectasis.

PARTICIPANTS:

Induced sputum samples were obtained from 112 adult patients with high-resolution CT scan-proven bronchiectasis and at least two exacerbations in the previous year, as part of an unrelated randomised control trial.

OUTCOME MEASURES:

Presence of null FUT2 polymorphisms were determined by gene sequencing and verified by endobronchial biopsy histochemical staining. Outcome measures were FEV1% predicted, exacerbation frequency, and bacterial, fungal and viral components of the microbiota (measured by culture independent approaches).

RESULTS:

Patients were grouped by FUT2 loss-of-function genotype; categorised as non-secretors (n=27, sese), heterozygous secretors (n=54, Sese) or homozygous secretors (n=31, SeSe). FEV1% was significantly lower in SeSe patients compared with sese patients (mean 61.6 (SD 20.0) vs 74.5 (18.0); p=0.023). Exacerbation frequency was significantly higher in SeSe (mean count 5.77) compared with sese (4.07; p=0.004) and Sese (4.63; p=0.026) genotypes. The time until first exacerbation was significantly shorter in SeSe compared with Sese (HR=0.571 (95% CI 0.343 to 0.950); p=0.031), with a similar trend for sese patients (HR=0.577 (0.311 to 1.07); p=0.081). sese had a significantly reduced frequency of Pseudomonas aeruginosa-dominated airway infection (8.7%) compared with Sese (31%; p=0.042) and SeSe (36%; p=0.035). In contrast, fungal, viral and non-dominant bacterial components of the microbiome were not significantly different between FUT2 genotypes.

CONCLUSIONS:

FUT2 genotype in patients with non-cystic fibrosis bronchiectasis was significantly associated with disease outcomes, with homozygous secretors exhibiting lower lung function, higher exacerbation number and a higher frequency of P. aeruginosa-dominated infection.

TRIAL REGISTRATION NUMBER:

ACTRN12609000578202 (anzctr.org.au); Pre-results.

KEYWORDS:

Bacterial Infection; Bronchiectasis; Viral infection

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