VKORC1 and CYP2C9 Polymorphisms: A Case Report in a Dutch Family with Pulmonary Fibrosis

Int J Mol Sci. 2019 Mar 7;20(5):1160. doi: 10.3390/ijms20051160.


Here, we describe a Dutch family with idiopathic pulmonary fibrosis (IPF). We hypothesized that there might be an association between the presence of Vitamin K epoxide reductase complex 1 (VKORC1) and/or cytochrome P450 2C9 (CYP2C9) variant alleles and the early onset of IPF in the members of this family. VKORC1 (rs9923231 and rs9934438) and CYP2C9 (rs1799853 and rs1057910) were genotyped in this family, which includes a significant number of pulmonary fibrosis patients. In all family members, at least one of the variant alleles tested was present. The presence of the VKORC1 variant alleles in all of the IPF cases and CYP2C9 variants in all but one, which likely leads to a phenotype that is characterized by the early onset and progressive course of IPF. Our findings indicate a role of these allelic variants in (familial) IPF. Therefore, we suggest that the presence of these variants, in association with other pathogenic mutations, should be evaluated during genetic counselling. Our findings might have consequences for the lifestyle of patients with familial IPF in order to prevent the disease from becoming manifest.

Keywords: familial idiopathic pulmonary fibrosis; oxidative stress; polymorphism; vitamin K supplementation.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Age of Onset
  • Aged, 80 and over
  • Cytochrome P-450 CYP2C9 / genetics*
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Idiopathic Pulmonary Fibrosis / genetics*
  • Male
  • Middle Aged
  • Netherlands
  • Pedigree
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic
  • Retrospective Studies
  • Vitamin K Epoxide Reductases / genetics*


  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases