case-control study, we evaluated the frequency of polymorphic variants in genes
of the apoptotic pathway in preeclamptic women in Southeast of Iran. We
identified a possible role of TP53-rs1042522, P21-rs1059234 and P21-rs1801270
gene polymorphisms in the development of preeclampsia. We found that GC and CC genotypes
of TP53-rs1042522 were associated with 0.5 and 0.4-Fold risk of PE in
Co-dominant and GG+GC genotype was associated with 1.6-Fold increased risk of
PE in recessive model. In addition, the CA genotype of P21-rs1801270 as a protective
factor was associated with 0.3-fold risk of PE in Co-dominant and Over-dominant
models and CA+AA genotype was associated with 0.4-fold risk of PE in Co-Dominant.
studies have already described the importance of polymorphic variants in genes
related to apoptotic pathways during pregnancy but these polymorphisms (TP53-rs1042522,
P21-rs1059234 and P21-rs1801270) have never been investigated as possible risk
factors for preeclampsia.
TP53 gene, some studies showed an association between SNPs of p53 gene and
idiopathic recurrent miscarriages18, recurrent
pregnancy loss19 and
Moradinasab et al. investigated the association between TP53 codon
72 polymorphisms, tobacco smoking, and breast cancer risk in southern Iranian
women from Bushehr. Their results suggested that TP53 Arg/Pro genotype modifies
the risk of breast cancer in tobacco smokers and causes significantly more
susceptibility to breast cancer due to smoking21. Yaghmaei et al. studied Tumor
protein p53 (Tp53) polymorphisms in Uterine Leiomyoma (UL) susceptibility in
southeastern Iran; they found the Pro/Pro genotype of Tp53 Arg72Pro
polymorphism was associated with UL susceptibility11. In these studies, similar to our
study in Iranian population, the CG genotype of TP53-rs1042522 was the most
prevalent genotype in women.
is no study about TP53 gene polymorphism and risk of PE in IRAN; Busatto et al.
analyzed the TP53-rs1042522 gene polymorphism in 119 preeclamptic women and 99
healthy pregnant women in Brazil. They found no significant difference between distribution
of the genotypic variants in cases and controls15.
Gao et al. isolated
and cultured human umbilical cord vein endothelial cells (HUVECs) from normal
and preeclampsia pregnancies in vitro and measured cell growth and flow
cytometric analysis to determine cell-cycle distribution and cell apoptosis. Their
results showed that the cell growth was significantly suppressed, accompanied
by the increased G1 arrest and apoptosis in cultured HUVECs from preeclampsia
pregnancies comparing with normotensive controls. Protein P53 was upregulated
in the cultured HUVECs from preeclampsia pregnancies, which induced G1 arrest,
followed by upregulating P21 expression, and downregulating cyclin E expression
and CDK2–cyclin E complexes22.
To the best of
our knowledge, there is no published report to examine the role of P21
polymorphisms and risk of PE. Although, Salimi et al. investigated the
association of p21 C98A (rs1801270) and C70T (rs1059234) polymorphisms and
Uterine leiomyoma (UL) in Iranian population. Their results showed that the CA
genotype of p21 C98A polymorphism was significantly higher in UL women so it
may be a risk factor for UL susceptibility12. In addition,
Taghavi et al. detected no significant differences between these polymorphisms
of P21 and risk of esophageal squamous cell carcinoma in northeastern Iran23. Similar to
our data, the CC genotype of rs1801270 and rs1059234 was more frequent genotype
and TT genotype of rs1801270 and AA genotype of rs1059234 are rare genotypes in
included multiple SNPs information, which are located in the same homologous
chromosome; the statistical power of haplotype analysis is stronger than the
analysis of single SNP24. In current study we
investigated the haplotype analysis of rs1801270 and rs1059234 polymorphisms of
P21 gene. Our results indicated that the TC
haplotype was significantly higher in PE patients and associated with 3.4-fold
increased risk of PE.
we evaluated the role of gene-gene interaction of TP53 and P21 polymorphisms
and their effects on PE development…..
conclusion, our results suggested that the TP53 and P21 polymorphisms influence
the risk of PE. Additional experiments on other SNPs and genes involved in
apoptosis are needed to understand the molecular events involved in PE.
Moreover, the influence of P53 and P21 variants on their mRNA stability,
expression and protein formation could help to investigation on PE pathology.
Thus, studies in different ethnic populations with larger sample size should be
performed to elucidate the molecular details of apoptosis in PE development.