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Editor's Note
April 2016

Nurturing Nature—Exploring the Possible Role of Epigenetics in Dyslipidemia

Author Affiliations
 

Copyright 2016 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA Cardiol. 2016;1(1):36. doi:10.1001/jamacardio.2015.0302

Whereas prior studies have suggested an association between both maternal adiposity and dysglycemia and adult offspring cardiometabolic health, there is a surprising paucity of data examining this same association for dyslipidemia. In this issue of JAMA Cardiology, Mendelson and colleagues1 look to start to fill that gap by investigating this association in the Framingham Heart Study. Using the prepregnancy parent low-density lipoprotein cholesterol (LDL-C) levels as a surrogate for peripartum LDL-C levels, they found that maternal, but not paternal, prepregnancy LDL-C level was strongly associated with adult offspring’s LDL-C level. After adjusting for known confounders and 37 known genetic loci related to LDL-C, for each 10-mg/dL higher level of the maternal prepregnancy LDL-C, the adult offspring’s LDL-C level was 3.2 mg/dL higher (to convert to millimoles per liter, multiply by 0.0259). In contrast, the paternal LDL-C was only 1.3 mg/dL higher.

What might explain this finding? As the investigators correctly note, this observed association does not prove causality. To that end, in this older Framingham Heart Study cohort, maternal dietary habits might have played a greater role than did paternal habits in setting the dietary habits of the offspring. Moreover, studies2 in the setting of familial hypercholesterolemia have not found any difference between maternal vs paternal carriage of familial hypercholesterolemia and offspring LDL-C levels, both in offspring with and those without familial hypercholesterolemia. However, there is a growing body of evidence that epigenetic regulation of gene expression can be influenced by environmental exposures. To that end, differential DNA methylation has been observed after periconceptional exposure to famine.3 Determining whether there are epigenetic transmission mechanisms underlying the observations seen in the study by Mendelson and colleagues1 will be an important next step. Regardless, this study should raise awareness of the effect of parental, and specifically maternal, hypercholesterolemia on the cardiovascular risk profile of offspring.

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Conflict of Interest Disclosures: Dr Sabatine has received research grant support through Brigham and Women’s Hospital from Amgen, AstraZeneca, Bristol-Myers Squibb, Daiichi-Sankyo, Eisai, GlaxoSmithKline, and Merck, and has served as a paid consultant for Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, Merck, Pfizer, Quest Diagnostics, and Sanofi.

References
1.
Mendelson  MM, Lyass  A, O’Donnell  CJ, D’Agostino  RB  Sr, Levy  D.  Association of maternal prepregnancy dyslipidemia with adult offspring dyslipidemia in excess of anthropometric, lifestyle, and genetic factors in the Framingham Heart Study [published online March 2, 2016].  JAMA Cardiol. doi:10.1001/jamacardio.2015.0304.Google Scholar
2.
Kusters  DM, Avis  HJ, Braamskamp  MJ,  et al.  Inheritance pattern of familial hypercholesterolemia and markers of cardiovascular risk.  J Lipid Res. 2013;54(9):2543-2549.PubMedGoogle ScholarCrossref
3.
Tobi  EW, Goeman  JJ, Monajemi  R,  et al.  DNA methylation signatures link prenatal famine exposure to growth and metabolism.  Nat Commun. 2014;5:5592.PubMedGoogle ScholarCrossref
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