title: Association between ACVR2A and early-onset preeclampsia: replication study in a Northeastern Brazilian population.
abstract: BACKGROUND
  Preeclampsia is a complex and heterogeneous disease with increased risk of maternal mortality, especially for earlier gestational onset. There is a great inconsistency regarding the genetics of preeclampsia across the literature. The gene Activin A receptor, type IIA (ACVR2A), was reported as associated to preeclampsia in Australian/New Zealand and Norwegian populations. The goal of this study was to validate this genetic association in a Brazilian population.
  
  
  METHODS
  We performed a case-control study using 693 controls and 613 cases (443 preeclampsia, 64 eclampsia and 106 HELLP syndrome), from a Northeastern Brazilian population. Five single nucleotide polymorphisms (SNPs) in ACVR2A were tested for association through multiple logistic regression models.
  
  
  RESULTS
  There was no statistical association with preeclampsia (per se), eclampsia or HELLP. However, by grouping preeclampsia in accordance to the gestational age at delivery, SNPs rs1424954 (OR = 1.86; 95% CI, 1.25-2.78; p = 0.002) and rs1014064 (OR = 1.77; 95% CI, 1.21-2.60; p = 0.004) were significantly associated with early onset preeclampsia (gestational age ≤ 34 weeks). The risk haplotype had a frequency of 0.468 in early preeclampsia compared to 0.316 in controls (p = 0.0008 and permuted p = 0.002).
  
  
  CONCLUSIONS
  Activin A receptors are important in decidualization, trophoblast invasion and placentation processes during pregnancy. The gene ACVR2A was associated with the more severe early onset preeclampsia. This finding supports the hypothesis of different pathogenic mechanisms contributing to the early- and late-onset preeclampsia.
authors.affiliation: Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, Brazil; Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: L C
authors.initials: LC
authors.lastname: Ferreira
authors.affiliation: Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, Brazil; Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: C E M
authors.initials: CE
authors.lastname: Gomes
authors.affiliation: Department of Obstetrics and Gynecology, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: A C P
authors.initials: AC
authors.lastname: Araújo
authors.affiliation: Maternidade Escola Januário Cicco, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: P F
authors.initials: PF
authors.lastname: Bezerra
authors.affiliation: Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA.
authors.forename: P
authors.initials: P
authors.lastname: Duggal
authors.affiliation: Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, Brazil; Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, Brazil; Institute of Science and Technology of Tropical Diseases (INCT-DT), Brazil. Electronic address: smbj@cb.ufrn.br.
authors.forename: S M B
authors.initials: SM
authors.lastname: Jeronimo
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005865:Gestational Age; D017359:HELLP Syndrome / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000453:epidemiology / Q000235:genetics*; D011247:Pregnancy; D055815:Young Adult
chemical_list: D030301:Activin Receptors, Type II; C425585:activin receptor type II-A
keywords: ACVR2A; Activin; Genetic association; Preeclampsia; SNP