The vitamin D binding protein (VTDB) is associated with both severity and outcome in women with lymphangioleiomyomatosis (LAM), according to new research published in the European Respiratory Journal.
The study included 101 women with LAM and 22 healthy controls from the National Centre for LAM in the UK. A second cohort of 152 women from the USA was used for replication and for a survival study. Researchers carried out genotyping studies with all participants, and mass spectrometry proteomics with 50 LAM patients and 20 controls.
The mass spectrometry proteomics approach was used to survey proteins from serum samples; 126 proteins were detected in all patients in the initial discovery cohort. Proteomic analysis showed VTDB was 2.6-fold lower in LAM than controls, and that VTDB was also lower in women with progressive LAM compared with stable LAM.
Genotyping studies showed that the allele frequencies of single nucleotide polymorphisms within three VTDB haplotypes were not different in LAM patients compared to the healthy controls, suggesting that genotype is not responsible for the lower VTDB levels in LAM versus controls.
The data also showed an association between VTDB genotype and median time of death or transplant, with a more rapid time to death or transplant in women with CC genotypes versus AA or AC; haplotypes of GC, the gene that encodes the VTDB protein, were also associated with the time to death or lung transplant.
The researchers say this suggests that VTDB is a novel biomarker of disease severity and clinical outcome in LAM, and that the GC genotype is the first genetic host factor found to influence transplant-free survival in LAM.
The findings are discussed in more detail in an accompanying editorial by Heng-Jia Liu and Elizabeth Henske, also published in the ERJ.