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Mutation in CYP27A1 identified in family with coronary artery disease

Kolsoum Inanloorahatloo1, Amir Farhang Zand Parsa, Klaus Huse

  • 1School of Biology, College of Science, University of Tehran, Tehran, Iran; Genome Analysis, Leibniz Institute for Age Research - Fritz Lipmann Institute, Jena, Germany.

European Journal of Medical Genetics
|October 2, 2013
PubMed

Insights

Genetic mutations in CYP27A1 may cause coronary artery disease (CAD). A specific mutation, p.Arg225His, was identified in a family with CAD, potentially impacting cholesterol transport and contributing to atherosclerosis.

Area of Science:

  • Genetics
  • Cardiovascular Medicine
  • Biochemistry

Background:

  • Coronary artery disease (CAD) is a major global health concern, with myocardial infarction as its most severe manifestation.
  • The genetic underpinnings of CAD remain largely elusive despite significant research efforts.
  • Understanding the genetic basis of CAD is crucial for developing targeted prevention and treatment strategies.

Purpose of the Study:

  • To identify the genetic cause of coronary artery disease (CAD) in a family with multiple affected individuals.
  • To investigate the role of the sterol 27-hydroxylase enzyme, encoded by CYP27A1, in the pathogenesis of CAD.
  • To explore potential mechanisms by which CYP27A1 mutations might contribute to CAD, focusing on vitamin D metabolism and reverse cholesterol transport.

Main Methods:

  • Whole exome sequencing was employed to identify genetic variants within the affected pedigree.
  • Vitamin D levels were measured to assess the impact of the identified mutation on this metabolic pathway.
  • Screening of the CYP27A1 gene in additional CAD patients was performed to evaluate the prevalence of potentially causative variations.

Main Results:

  • A novel mutation, CYP27A1 p.Arg225His, was identified as the likely cause of CAD in the studied family.
  • Measurements indicated that the p.Arg225His mutation does not appear to affect CAD through alterations in vitamin D levels.
  • The study suggests that the mutation may contribute to CAD by disrupting reverse cholesterol transport (RCT).
  • Four additional potentially harmful CYP27A1 variations were found in seven unrelated CAD patients, suggesting a broader role in the disease.

Conclusions:

  • The identified CYP27A1 p.Arg225His mutation is strongly implicated as a cause of CAD in the studied family, likely through impaired reverse cholesterol transport.
  • The findings suggest that variations in CYP27A1, the gene responsible for cerebrotendinous xanthomatosis, may represent a previously unrecognized genetic risk factor for early-onset atherosclerosis and CAD.
  • Further research is warranted to elucidate the precise mechanisms by which CYP27A1 dysfunction contributes to CAD and to explore its clinical significance in broader patient populations.

Keywords:
CYP27A1Coronary artery diseaseExome sequencingReverse cholesterol transport

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