RT Journal Article
SR Electronic
T1 The vitamin D binding protein axis modifies disease severity in lymphangioleiomyomatosis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1800951
DO 10.1183/13993003.00951-2018
VO 52
IS 5
A1 Suzanne Miller
A1 Clare Coveney
A1 Janice Johnson
A1 Aliki-Eleni Farmaki
A1 Nishant Gupta
A1 Martin D. Tobin
A1 Louise V. Wain
A1 Francis X. McCormack
A1 David J. Boocock
A1 Simon R. Johnson
YR 2018
UL http://erj.ersjournals.com/content/52/5/1800951.abstract
AB 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.The vitamin D binding protein and GC genotype are associated with lung function and survival in women with LAM http://ow.ly/UacI30leLzr