IJMEG Copyright © 2010-present. All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Mol Epidemiol Genet 2012;3(3):228-236

Original Article
A case-control study of maternal blood mitochondrial DNA copy number and
preeclampsia risk

Chunfang Qiu, Karin Hevner, Daniel A Enquobahrie, Michelle A Williams

Center for Perinatal Studies, Swedish Medical Center, Seattle Washington, USA; Department of Epidemiology, School of Public
Health, University of Washington, Seattle, Washington, USA; Department of Epidemiology, Harvard School of Public Health,
Boston, Massachusetts, USA

Received July 16, 2012; accepted August 21, 2012; Epub August 31 , 2012; Published September 15, 2012

Abstract: A growing body of evidence suggests that mitochondrial dysfunction is associated with oxidative stress and impaired
differentiation and invasion of trophoblasts, both of which have been related to preeclampsia pathogenesis. However, studies
that examined circulating mitochondrial DNA (mtDNA) copy number in relation to preeclampsia are limited. Therefore, we
examined association of maternal whole blood mtDNA copy number (a novel biomarker of systemic mitochondrial dysfunction)
with the odds of preeclampsia. This case-control study was comprised of 144 preeclampsia cases and 407 normotensive
controls. Real-time quantitative polymerase chain reaction (PCR) was used to assess the relative copy number of mtDNA in
maternal whole blood samples collected at delivery. Logistic regression procedures were used to estimate adjusted odds
ratios (OR) and 95% confidence intervals (CI). Median mtDNA copy number was significantly higher among preeclamptic
women compared with controls (271.5 vs. 239.3, Mann-Whitney U test p-value <0.001). There was evidence of a linear trend in
higher odds of preeclampsia with increasing quartiles of mtDNA copy number (P for trend=0.03) after controlling for
confounders. The adjusted ORs for the successive quartiles of mtDNA copy number, compared with the referent (first quartile)
were 1.30 (95%CI 0.66-2.56), 1.93 (95%CI 1.02-3.67) and 1.86 (95%CI 1.00-3.48). Our findings suggest that maternal
mitochondrial dysfunction may contribute to the pathogenesis of preeclampsia. However, replication in prospective studies is
needed to further investigate this relationship. (IJMEG1207004).

Keywords: Mitochondria, DNA, mitochondrial DNA, preeclampsia, pregnancy

Address all correspondence to:
Dr. Chunfang Qiu
Swedish Medical Center
Center for Perinatal Studies
1124 Columbia Street, Suite 750
Seattle, WA 98104, USA.
Tel: (206) 215-3053; Fax: (206) 215-6995
E-mail: Chun-fang.Qiu@Swedish.org