Preeclampsia (PE), asmultisystem pathological condition that occurs in 3–5% of pregnant women worldwide,is clinically diagnosed by maternal hypertension and proteinuria 1, 2.
Preeclampsia may progress toeclampsia (convulsive form) due to late presentation, delayed diagnosis, anddelayed treatment; therefore, there is a need to identify reliable hallmarksfor the early diagnosis of preeclampsia and to develop efficient treatmentstrategies3.In spite ofextensive research, the precise pathogenic mechanisms underlying preeclampsiais still undetermined. However, immune maladaptation, inadequate placentaldevelopment and trophoblast invasion, placental ischemia, oxidative stress, andthrombosis are all thought to represent key factorsin the development of the disease. Furthermore, these components have geneticfactors that may be involved in these pathogenic changes4.Proliferationand apoptosis (programmed cell death) are absolutely necessary components ofthe trophoblast life cycle. There are aberrant cell turnover including anincreased apoptosis in placental trophoblast of preeclamptic pregnancies5.
Abnormaldifferentiation of cytotrophoblast cells during their invasion of thespiral uterinearteries results in a decreased placental size and restrictedutero-placental blood flow, which does not meet the needs of the growing fetus.As a consequence, hypoxia of the placenta isfollowed by an increase in syncytiotrophoblast apoptosis and necrosis6. The preciseintracellular mechanisms that promote apoptosis in PE are unknown7. TP53, as atumor-suppressor gene, is a key component in cell cycle progression and theinduction of apoptosis8. P53 proteinis an important transcription factor that regulates growth arrest, apoptosisand DNA repair under cell stress conditions, and then it is phosphorylated andacetylated at multiple sites to activate downstream target genes9. It was shownthat the level of p53 was increased in placentas during complicated pregnancies;this finding highlighted the role of P53 in trophoblast apoptosis10. The increasedlevels of p53, promotes the downstream transcription of elements involved inapoptosis and cell-cycle arrest, including p21, a cyclin-dependent kinaseinhibitor7.
The TP53 geneis located on chromosome 17 and encodes a 53 kDa protein containing 393 aminoacids. The TP53 gene has various single nucleotide polymorphisms (SNPs) withprobable functional effects. Awell-recognized polymorphism in TP53 gene (P72R, rs1042522) is characterized bya G>C substitution at codon 72 and is located in the transactivation domainof the p53 protein that could affect activity of this protein11.The mostcommonly studied polymorphism of p21 gene is serine to arginine replacement inthe codon31 of P21 protein (rs1801270, C98A).
This substitution affects the DNAbinding zinc finger motif and may alter expression and activity of p21. Anotherp21 polymorphism rs1059234 (C70T) located 20 nucleotides downstream of the stopcodon within the 3’untranslated region. It is considered that, this region isan important site for cell differentiation, proliferation, and tumorsuppression12. Although severalstudies have suggested the importance of the apoptosis pathways and its relatedgenes in the regulation of PE13, 14; there is nostudies evaluating polymorphisms in P21 gene and correlation with PEdevelopment. In addition, the published reports on the association between P53gene polymorphisms and PE are sparse in number15. In thisstudy, we analyzed the frequencies of TP53 (rs1042522, P72R) and P21 (rs1801270,C98A and rs1059234, C70T) genes polymorphisms and their role as risk factorsfor PE development.