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Suzanne Miller
Suzanne
Miller
Clare Coveney
Clare
Coveney
Janice Johnson
Janice
Johnson
Aliki-Eleni Farmaki
Aliki-Eleni
Farmaki
Nishant Gupta
Nishant
Gupta
Martin D. Tobin
Martin D.
Tobin
Louise V. Wain
Louise V.
Wain
Francis X. McCormack
Francis X.
McCormack
David J. Boocock
David J.
Boocock
Simon R. Johnson
Simon R.
Johnson
The Vitamin D Binding Protein axis modifies disease severity in Lymphangioleiomyomatosis
University of Leicester
2019
IR content
2019-03-19 11:36:38
Journal contribution
https://figshare.le.ac.uk/articles/journal_contribution/The_Vitamin_D_Binding_Protein_axis_modifies_disease_severity_in_Lymphangioleiomyomatosis/10213997
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.