Mutation in CYP27A1 identified in family with coronary artery disease

Eur J Med Genet. 2013 Dec;56(12):655-60. doi: 10.1016/j.ejmg.2013.09.008. Epub 2013 Sep 28.


Coronary artery disease (CAD) is a leading cause of death worldwide. Myocardial infarction is the most severe outcome of CAD. Despite extensive efforts, the genetics of CAD is poorly understood. We aimed to identify the genetic cause of CAD in a pedigree with several affected individuals. Exome sequencing led to identification of a mutation in CYP27A1 that causes p.Arg225His in the encoded protein sterol 27-hydroxylase as the likely cause of CAD in the pedigree. The enzyme is multifunctional, and several of its functions including its functions in vitamin D metabolism and reverse cholesterol transport (RCT) are relevant to the CAD phenotype. Measurements of vitamin D levels suggested that the mutation does not affect CAD by affecting this parameter. We suggest that the mutation may cause CAD by affecting RCT. Screening of all coding regions of the CYP27A1 in 100 additional patients led to finding four variations (p.Arg14Gly, p.Arg26Lys, p.Ala27Arg, and p.Val86Met) in seven patients that may contribute to their CAD status. CYP27A1 is the known causative gene of cerebrotendinous xanthomatosis, a disorder which is sometimes accompanied by early onset atherosclerosis. This and the observation of potentially harmful variations in unrelated CAD patients provide additional evidence for the suggested causative role of the p.Arg225His mutation in CAD.

Keywords: CYP27A1; Coronary artery disease; Exome sequencing; Reverse cholesterol transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Case-Control Studies
  • Cholestanetriol 26-Monooxygenase / genetics*
  • Cholesterol / blood
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / genetics*
  • Exome
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Pedigree
  • Vitamin D / blood


  • Vitamin D
  • Cholesterol
  • CYP27A1 protein, human
  • Cholestanetriol 26-Monooxygenase