Increased protein-coding mutations in the mitochondrial genome of African American women with preeclampsia.
Preeclampsia occurs more frequently in women of African ancestry. The cause of this hypertensive complication is unclear, but placental oxidative stress may play a role. Because mitochondria are the major sites of oxidative phosphorylation, we hypothesized that placentas of preeclamptic pregnancies harbor mitochondrial DNA (mtDNA) mutations. Next-generation sequencing of placental mtDNA in African American preeclamptics (N = 30) and controls (N = 38) from Chicago revealed significant excesses in preeclamptics of nonsynonymous substitutions in protein-coding genes and mitochondrially encoded nicotinamide adenine dinucleotide dehydrogenase 5 gene and an increase in the substitution rate (P = .0001). Moreover, 88% of preeclamptics and 53% of controls carried at least one nonsynonymous substitution (P = .005; odds ratio [OR] = 6.36, 95% confidence interval [CI]: 1.5-39.1). These results were not replicated in a sample of African American preeclamptics (N = 162) and controls (N = 171) from Detroit. Differences in study design and heterogeneity may account for this lack of replication. Nonsynonymous substitutions in mtDNA may be risk factors for preeclampsia in some African American women, but additional studies are required to establish this relationship.
Department of Obstetrics and Gynecology, The University of Chicago, Chicago, IL 60637, USA.
David
D
Ding
Nicole M
NM
Scott
Emma E
EE
Thompson
Tinnakorn
T
Chaiworapongsa
Raul
R
Torres
Christine
C
Billstrand
Kathleen
K
Murray
Phillip J
PJ
Dexheimer
Mahmoud
M
Ismail
Helen
H
Kay
Shawn
S
Levy
Roberto
R
Romero
Marshall D
MD
Lindheimer
Dan L
DL
Nicolae
Carole
C
Ober
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D002641:Chicago; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D005260:Female; D020022:Genetic Predisposition to Disease; D054629:Genome, Mitochondrial; D006239:Haplotypes; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009245:NADH Dehydrogenase / Q000235:genetics; D011225:Pre-Eclampsia / Q000208:ethnology / Q000235:genetics*; D011247:Pregnancy; D017422:Sequence Analysis, DNA; D014327:Trophoblasts / Q000737:chemistry; D014470:Umbilical Cord / Q000737:chemistry; D055815:Young Adult
D004272:DNA, Mitochondrial; D009245:NADH Dehydrogenase