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Am J Hypertens. 2015 Jul;28(7):915-23. doi: 10.1093/ajh/hpu242. Epub 2014 Dec 17.

Genetic Predisposition to Dyslipidemia and Risk of Preeclampsia.

Author information

1
Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa, USA; Present address: Department of Genetics, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
2
Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa, USA;
3
Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island, USA;
4
Center for Human Genetic Research and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA; Program in Medical and Population Genetics, Broad Institute , Cambridge, Massachusetts, USA;
5
Department of Surgery, Penn Transplant Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA;
6
Department of Biostatistics, University of Iowa College of Public Health, Iowa City, Iowa, USA;
7
Division of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA;
8
Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA.
9
Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa, USA; kelli-ryckman@uiowa.edu.

Abstract

BACKGROUND:

Large epidemiologic studies support the role of dyslipidemia in preeclampsia; however, the etiology of preeclampsia or whether dyslipidemia plays a causal role remains unclear. We examined the association between the genetic predisposition to dyslipidemia and risk of preeclampsia using validated genetic markers of dyslipidemia.

METHODS:

Preeclampsia cases (n = 164) and normotensive controls (n = 110) were selected from live birth certificates to nulliparous Iowa women during the period August 2002 to May 2005. Disease status was verified by medical chart review. Genetic predisposition to dyslipidemia was estimated by 4 genetic risk scores (GRS) (total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides) on the basis of established loci for blood lipids. Logistic regression analyses were used to evaluate the relationships between each of the 4 genotype scores and preeclampsia. Replication analyses were performed in an independent, US population of preeclampsia cases (n = 516) and controls (n = 1,097) of European ancestry.

RESULTS:

The GRS related to higher levels of TC, LDL-C, and triglycerides demonstrated no association with the risk of preeclampsia in either the Iowa or replication population. The GRS related to lower HDL-C was marginally associated with an increased risk for preeclampsia (odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.99-1.07; P = 0.10). In the independent replication population, the association with the HDL-C GRS was also marginally significant (OR = 1.03, 95% CI: 1.00-1.06; P = 0.04).

CONCLUSIONS:

Our data suggest a potential effect between the genetic predisposition to dyslipidemic levels of HDL-C and an increased risk of preeclampsia, and, as such, suggest that dyslipidemia may be a component along the causal pathway to preeclampsia.

KEYWORDS:

blood pressure; dyslipidemia; genetic epidemiology; genetic risk score; hypertension; preeclampsia.

PMID:
25523295
PMCID:
PMC4542907
DOI:
10.1093/ajh/hpu242
[Indexed for MEDLINE]
Free PMC Article

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