Nrf2 rs6721961 and Oxidative Stress in Preeclampsia: Association withthe Risk of Preeclampsia and Early-Onset Preeclampsia

Preeclampsia as a multifactor hypertensive disorder of pregnancy is associated with enhanced
placental oxidative stress. The Keap1-Nrf2 pathway protects cells against oxidative stress. We
examined the possible association between the Nrf2 variants in relation to oxidative stress
parameters with the risk of preeclampsia. We studied 150 preeclampsia women and 150 women
with a normal pregnancy to find the frequency of Nrf2 rs6721961 genotypes using the PCRRFLP
method. Also, an association between the Nrf2 genotypes with the levels of
malondialdehyde (MDA) and total antioxidant capacity (TAC) was analyzed. Significantly
lower TAC and higher MDA levels were found in preeclampsia patients compared to controls
(P<0.0001). For the first time, we report an association between the Nrf2 rs6721961
polymorphism and preeclampsia risk. The present study indicated that the GT genotype and the
T allele of the Nrf2 rs6721961 increased the risk of preeclampsia by 2.81 and 2.39 times,
respectively. Also, the Nrf2 TT genotype was associated with a 3.9-fold increased risk of earlyonset
preeclampsia. We detected a positive association between the levels of body mass index,
MDA, and the Nrf2 polymorphism with the risk of preeclampsia and a negative correlation
between the level of TAC with the preeclampsia risk. Also, an association between the
rs6721961 TT genotype with higher serum MDA levels was found. Our study suggests
oxidative stress is involved in the pathogenesis of preeclampsia and the Nrf2 rs6721961
polymorphism through alteration in the levels of oxidative stress parameters might increase the
risk of preeclampsia and early-onset preeclampsia.