title: Association between estrogen receptor alpha (ESR1) gene polymorphisms and severe preeclampsia.
abstract: Associations have been reported between estrogen receptor alpha (ESR1) gene polymorphisms and various pathological conditions, including cardiovascular diseases. Our aim was to investigate whether two polymorphisms of the ESR1 gene (ESR1 c.454 -397T>C: PvuII restriction site and c.454 -351A>G: XbaI restriction site) are associated with preeclampsia. In a case-control study, we analyzed blood samples from 119 severely preeclamptic patients and 103 normotensive, healthy pregnant women using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. All of the women were Caucasian. There was no association between severe preeclampsia and the PvuII and XbaI ESR1 gene polymorphisms separately. However, with the simultaneous carriage of both polymorphisms, the TT/AA genotype combination was significantly more frequent in severely preeclamptic patients than in healthy control subjects (24.4% vs. 9.7%, p=0.003), whereas the TT/AG combination was significantly less frequent in the severely preeclamptic group than in the control group (5.0% vs. 18.4%, p=0.002). According to the haplotype estimation, the homozygous T-A haplotype carriers had an increased risk of severe preeclampsia independent of maternal age, prepregnancy BMI, primiparity and smoking status (adjusted odds ratio [OR]: 4.36, 95% confidence interval [CI]: 1.65-11.53). The GG genotype of the XbaI polymorphism was associated with a lower risk of fetal growth restriction in patients with severe preeclampsia (OR: 0.23, 95% CI: 0.07-0.73). In conclusion, the homozygous T-A haplotype carriers of ESR1 PvuII and XbaI polymorphisms showed an increased risk of severe preeclampsia. In addition, the GG genotype of the XbaI polymorphism decreased the risk of fetal growth restriction in severely preeclamptic patients.
authors.affiliation: Department of Obstetrics and Gynecology, Kútvölgyi Clinical Center, Semmelweis University, Budapest, Hungary. molvarec@freemail.hu
authors.forename: Attila
authors.initials: A
authors.lastname: Molvarec
authors.forename: Agota
authors.initials: A
authors.lastname: Vér
authors.forename: Andrea
authors.initials: A
authors.lastname: Fekete
authors.forename: Klára
authors.initials: K
authors.lastname: Rosta
authors.forename: László
authors.initials: L
authors.lastname: Derzbach
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Derzsy
authors.forename: István
authors.initials: I
authors.lastname: Karádi
authors.forename: János
authors.initials: J
authors.lastname: Rigó
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D012150:Polymorphism, Restriction Fragment Length; D011225:Pre-Eclampsia / Q000235:genetics* / Q000503:physiopathology; D011247:Pregnancy; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D047628:Estrogen Receptor alpha; D004247:DNA