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Genetics of Familial Hypercholesterolemia

  • New Drugs Approved for Homozygous FH (SS Virani, Section Editor)
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Abstract

Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein (LDL) cholesterol and premature cardiovascular disease, with a prevalence of approximately 1 in 200–500 for heterozygotes in North America and Europe. Monogenic FH is largely attributed to mutations in the LDLR, APOB, and PCSK9 genes. Differential diagnosis is critical to distinguish FH from conditions with phenotypically similar presentations to ensure appropriate therapeutic management and genetic counseling. Accurate diagnosis requires careful phenotyping based on clinical and biochemical presentation, validated by genetic testing. Recent investigations to discover additional genetic loci associated with extreme hypercholesterolemia using known FH families and population studies have met with limited success. Here, we provide a brief overview of the genetic determinants, differential diagnosis, genetic testing, and counseling of FH genetics.

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Notes

  1. Note: For the purposes of this article, it can be assumed that “FH” refers to the heterozygous state as it is the more common form of FH; homozygous FH (HoFH) will be specified in the text.

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Acknowledgements

We would like to acknowledge Ashley Kuharchik (CPhT) for the use of her graphic design skills. We would also like to thank Ingrid Glurich, PhD and Marie Fleisner for their editorial assistance in preparing this manuscript.

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Conflict of Interest

Ariel Brautbar, Emili Leary, Kristen Rasmussen, Don P. Wilson, Robert D. Steiner, and Salim Virani declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Division of Genetics, Cook Children’s Medical Center, Fort Worth, TX, USA

    Ariel Brautbar

  2. Department of Medicine, Baylor College of Medicine, 6565 Fannin Street, Houston, TX, 77030, USA

    Ariel Brautbar

  3. Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA

    Ariel Brautbar

  4. School of Pharmacy, University of Wisconsin—Madison, Madison, WI, USA

    Emili Leary

  5. Clinical Pharmacy Services, Marshfield Clinic, Marshfield, WI, USA

    Emili Leary

  6. Center for Human Genetics, Marshfield Clinic, Marshfield, WI, USA

    Kristen Rasmussen

  7. Division of Pediatric Endocrinology & Diabetes, Cook Children’s Medical Center, Fort Worth, TX, USA

    Don P. Wilson

  8. Marshfield Clinic Research Foundation, Marshfield, WI, USA

    Robert D. Steiner

  9. Department of Pediatrics, University of Wisconsin, Madison, WI, USA

    Robert D. Steiner

  10. Michael E. DeBakey Veterans Affairs Medical Center and Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Salim Virani

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  1. Ariel Brautbar
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  2. Emili Leary
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  3. Kristen Rasmussen
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  4. Don P. Wilson
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  5. Robert D. Steiner
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  6. Salim Virani
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Corresponding author

Correspondence to Ariel Brautbar.

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This article is part of the Topical Collection on New Drugs Approved for Homozygous FH

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Brautbar, A., Leary, E., Rasmussen, K. et al. Genetics of Familial Hypercholesterolemia. Curr Atheroscler Rep 17, 20 (2015). https://doi.org/10.1007/s11883-015-0491-z

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