Human genetic insights into lipoproteins and risk of cardiometabolic disease.

TitleHuman genetic insights into lipoproteins and risk of cardiometabolic disease.
Publication TypeJournal Article
Year of Publication2017
AuthorsStitziel, NO
JournalCurr Opin Lipidol
Volume28
Issue2
Pagination113-119
Date Published2017 Apr
ISSN1473-6535
KeywordsCardiovascular Diseases, Genetic Predisposition to Disease, Humans, Lipoproteins, Risk
Abstract

PURPOSE OF REVIEW: Human genetic studies have been successfully used to identify genes and pathways relevant to human biology. Using genetic instruments composed of loci associated with human lipid traits, recent studies have begun to clarify the causal role of major lipid fractions in risk of cardiometabolic disease.

RECENT FINDINGS: The causal relationship between LDL cholesterol and coronary disease has been firmly established. Of the remaining two major fractions, recent studies have found that HDL cholesterol is not likely to be a causal particle in atherogenesis, and have instead shifted the causal focus to triglyceride-rich lipoproteins. Subsequent results are refining this view to suggest that triglycerides themselves might not be causal, but instead may be a surrogate for the causal cholesterol content within this fraction. Other studies have used a similar approach to address the association between lipid fractions and risk of type 2 diabetes. Beyond genetic variation in the target of statin medications, reduced LDL cholesterol associated with multiple genes encoding current or prospective drug targets associated with increased diabetic risk. In addition, genetically lower HDL cholesterol and genetically lower triglycerides both appear to increase risk of type 2 diabetes.

SUMMARY: Results of these and future human genetic studies are positioned to provide substantive insights into the causal relationship between lipids and human disease, and should highlight mechanisms with important implications for our understanding of human biology and future lipid-altering therapeutic development.

DOI10.1097/MOL.0000000000000389
Alternate JournalCurr Opin Lipidol
PubMed ID28059951
PubMed Central IDPMC5584563
Grant ListK08 HL114642 / HL / NHLBI NIH HHS / United States
R01 HL131961 / HL / NHLBI NIH HHS / United States
UM1 HG008853 / HG / NHGRI NIH HHS / United States