The vitamin D binding protein axis modifies disease severity in lymphangioleiomyomatosis

Miller, S., Coveney, C., Johnson, J., Farmaki, A., Gupta, N., Tobin, M.D., Wain, L.V., McCormack, F.X., Boocock, D.J. ORCID: 0000-0002-7333-3549 and Johnson, S.R., 2018. The vitamin D binding protein axis modifies disease severity in lymphangioleiomyomatosis. European Respiratory Journal, 52 (5): 1800951. ISSN 0903-1936

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Abstract

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.

Item Type: Journal article
Publication Title: European Respiratory Journal
Creators: Miller, S., Coveney, C., Johnson, J., Farmaki, A., Gupta, N., Tobin, M.D., Wain, L.V., McCormack, F.X., Boocock, D.J. and Johnson, S.R.
Publisher: European Respiratory Society
Date: 1 November 2018
Volume: 52
Number: 5
ISSN: 0903-1936
Identifiers:
NumberType
10.1183/13993003.00951-2018UNSPECIFIED
Rights: Copyright ©ERS 2018. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.
Divisions: Schools > School of Science and Technology
Depositing User: Jonathan Gallacher
Date Added: 01 Aug 2018 09:52
Last Modified: 05 Nov 2018 15:03
URI: http://irep.ntu.ac.uk/id/eprint/34212

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