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The Vitamin D Binding Protein axis modifies disease severity in Lymphangioleiomyomatosis

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posted on 19.03.2019, 11:36 by Suzanne Miller, Clare Coveney, Janice Johnson, Aliki-Eleni Farmaki, Nishant Gupta, Martin D. Tobin, Louise V. Wain, Francis X. McCormack, David J. Boocock, Simon R. Johnson
Lymphangioleiomyomatosis (LAM) is a rare disease of women. Decline in lung function is variable, making appropriate targeting of therapy difficult. We used unbiased serum proteomics to identify markers associated with outcome in LAM. 101 women with LAM and 22 healthy controls were recruited from the National Centre for LAM in the UK. 152 DNA and serum samples with linked lung function and outcome data were obtained from patients in the National Heart, Lung and Blood Institute LAM Registry in the USA. Proteomic analysis was performed on a discovery cohort of 50 LAM and 20 control serum samples using a SCIEX SWATH mass spectrometric workflow. Protein levels were quantitated by ELISA and single nucleotide polymorphisms in GC (group-specific component) encoding vitamin D binding protein (VTDB) were genotyped. Proteomic analysis showed VTDB was 2.6-fold lower in LAM than controls. Serum VTDB was lower in progressive compared with stable LAM (p=0.001) and correlated with diffusing capacity of the lung for carbon monoxide (p=0.01). Median time to death or lung transplant was reduced by 46 months in those with CC genotypes at rs4588 and 38 months in those with non-A-containing haplotypes at rs7041/4588 (p=0.014 and 0.008, respectively). The VTDB axis is associated with disease severity and outcome, and GC genotype could help predict transplant-free survival in LAM.

History

Citation

European Respiratory Journal

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Health Sciences

Version

VoR (Version of Record)

Published in

European Respiratory Journal

Publisher

European Respiratory Society: ERJ (Wiley)

eissn

1399-3003

Acceptance date

29/07/2018

Copyright date

2018

Available date

19/03/2019

Publisher version

https://erj.ersjournals.com/content/52/5/1800951

Language

en

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