L C Ferreira1, C E M Gomes2, A C P Araújo3, P F Bezerra4, P Duggal5, S M B Jeronimo6. 1. 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. 2. 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. 3. Department of Obstetrics and Gynecology, Federal University of Rio Grande do Norte, Natal, Brazil. 4. Maternidade Escola Januário Cicco, Federal University of Rio Grande do Norte, Natal, Brazil. 5. Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA. 6. 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.
Abstract
INTRODUCTION: 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). DISCUSSION: 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.
INTRODUCTION: 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). DISCUSSION: 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: Eliza C Miller; Ashley Wilczek; Natalie A Bello; Sarah Tom; Ronald Wapner; Yousin Suh Journal: Ageing Res Rev Date: 2021-12-03 Impact factor: 10.895