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2017 ; 12
(6
): e0180065
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Double hit of NEMO gene in preeclampsia
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Sakowicz A
; Pietrucha T
; Rybak-Krzyszkowska M
; Huras H
; Gach A
; Sakowicz B
; Banaszczyk M
; Grzesiak M
; Biesiada L
PLoS One
2017[]; 12
(6
): e0180065
PMID28654673
show ga
The precise etiology of preeclampsia is unknown. Family studies indicate that
both genetic and environmental factors influence its development. One of these
factors is NFkB, whose activation depends on NEMO (NFkB essential modulator. This
is the first study to investigate the association between the existence of single
nucleotide variant of the NEMO gene and the appearance of preeclampsia. A total
of 151 women (72 preeclamptic women and 79 controls) and their children were
examined. Sanger sequencing was performed to identify variants in the NEMO gene
in the preeclamptic mothers. The maternal identified variants were then sought in
the studied groups of children, and in the maternal and child controls, using
RFLP-PCR. Real-time RT-PCR was performed to assess NEMO gene expression in
maternal blood, umbilical cord blood and placentas. The sequencing process
indicated the existence of two different variants in the 3'UTR region of the NEMO
gene of preeclamptic women (IKBKG:c.*368C>A and IKBKG:c.*402C>T). The
simultaneous occurrence of the TT genotype in the mother and the TT genotype in
the daughter or a T allele in the son increased the risk of preeclampsia
development 2.59 fold. Additionally, we found that the configuration of
maternal/fetal genotypes (maternal TT/ daughter TT or maternal TT/son T) of
IKBKG:c.*402C/T variant is associated with the level of NEMO gene expression. Our
results showed that, the simultaneous occurrence of the maternal TT genotype
(IKBKG:c.*402C>T variants) and TT genotype in the daughter or T allele in the son
correlates with the level of NEMO gene expression and increases the risk of
preeclampsia development. Our observations may offer a new insight into the
genetic etiology and pathogenesis of preeclampsia.
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