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Curr Opin Pulm Med. 2018 May;24(3):287-295. doi: 10.1097/MCP.0000000000000467.

Pharmacogenetic variants and vitamin K deficiency: a risk factor or trigger for fibrosing interstitial pneumonias?

Drent M1,2,3, Wijnen P3,4, Bast A1,3,5.

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Department of Pharmacology and Toxicology, Faculty of Health, Medicine and Life Science, Maastricht University, Maastricht.
ILD Center of Excellence, Department of Respiratory Medicine, St. Antonius Hospital, Nieuwegein.
ILD Care Foundation Research Team, Ede.
Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht.
Venlo Campus, Maastricht University, Venlo, The Netherlands.



Fibrosing interstitial pneumonias are associated with various stages of fibrosis. The cause of this group of syndromes remains largely unknown. For most of these diseases, a genetic basis, environmental factors and certain triggers have been suggested as possible risk factors. Various studies have found an association between genetic polymorphisms, or the presence of certain variant alleles, and the occurrence and/or progression of interstitial pneumonias of unknown origin. An acute exacerbation of idiopathic pulmonary fibrosis shows characteristics of diffuse alveolar haemorrhage (DAH). DAH can be aggravated by vitamin K deficiency. This review deals with pharmacogenetic factors underlying interindividual differences of vitamin K status in patients with interstitial pneumonias and the possibilities for a personalized approach to patient management.


DAH has been associated with the presence of variant alleles in vitamin K epoxide reductase complex 1, cytochrome P450 (CYP)2C9 and CYP2C19 genes. Vitamin K deficiency has been associated with an increased risk for the development of DAH and progression and/or deterioration of interstitial pneumonias. This is in line with plausible pathophysiological mechanisms. However, clinical use should be confirmed.


DAH has been associated with vitamin K deficiency and suggested as potential trigger of fibrosing interstitial pneumonias. Information on genetic variation might benefit ongoing/new clinical trials, design of which should reflect needs to address relevance of testing gene variants. Whether vitamin K supplementation may prevent exacerbations or progression of interstitial pneumonias needs to be explored in future studies.

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