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Maternal inheritance of familial hypercholesterolemia caused by the V408M low-density lipoprotein receptor mutation

Jorie Versmissen1, Ilse P G Botden, Roeland Huijgen

  • 1Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

Atherosclerosis
|September 20, 2011
PubMed

Insights

Familial hypercholesterolemia (FH) inherited from mothers leads to significantly higher mortality than when inherited from fathers. This supports the fetal origin of adult disease, highlighting the need for maternal cholesterol management during pregnancy.

Area of Science:

  • Cardiovascular Genetics
  • Developmental Biology
  • Epidemiology

Background:

  • Maternal hypercholesterolemia during fetal development can increase atherosclerosis risk.
  • Familial hypercholesterolemia (FH) is an inherited condition causing high LDL cholesterol.
  • The impact of maternal vs. paternal inheritance of FH on long-term health outcomes is not fully understood.

Purpose of the Study:

  • To investigate whether the parent of origin of familial hypercholesterolemia (FH) influences mortality risk.
  • To test the hypothesis that maternal inheritance of FH is associated with more extreme CHD risk.

Main Methods:

  • Analysis of a large Dutch pedigree with a known LDL receptor gene mutation (V408M).
  • Studied 161 individuals across seven generations with known FH status and parental origin.
  • Calculated standardized mortality ratios (SMR) and used Poisson regression to compare maternal and paternal FH inheritance.

Main Results:

  • Maternal FH inheritance showed a significantly higher excess mortality (SMR 2.49) compared to paternal inheritance (SMR 1.30).
  • Relative risk of excess mortality was 2.2 for maternal inheritance (p=0.048).
  • Paternal FH inheritance did not show a statistically significant increase in mortality.

Conclusions:

  • Inheriting familial hypercholesterolemia (FH) from the mother is linked to substantially increased all-cause mortality.
  • Findings support the fetal origin of adult disease hypothesis, emphasizing prenatal influences on atherosclerosis.
  • Further research is needed on safe cholesterol-lowering therapies for pregnant women with FH to mitigate adverse epigenetic effects in offspring.
Abstract

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