| Title: | The vitamin D binding protein axis modifies disease severity in lymphangioleiomyomatosis |
| Journal: | European Respiratory Journal |
| Published: | 9 Aug 2018 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30093573/ |
| DOI: | https://doi.org/10.1183/13993003.00951-2018 |
| URL: | https://erj.ersjournals.com/content/erj/52/5/1800951.full.pdf |
Publication 8556
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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.</p>
10 Authors
- 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
1 Application
| Application ID | Title |
|---|---|
| 648 | Common and rare genetic variants in respiratory health: the UK Biobank Lung Exome Variant Evaluation (UK BiLEVE) consortium |
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