Genetic association of ERAP1 and ERAP2 with eclampsia and preeclampsia in northeastern Brazilian women

Sci Rep. 2021 Mar 24;11(1):6764. doi: 10.1038/s41598-021-86240-z.

Abstract

The clinical spectrum of hypertensive disorders of pregnancy (HDP) is determined by the interplay between environmental and genetic factors, most of which remains unknown. ERAP1, ERAP2 and LNPEP genes code for multifunctional aminopeptidases involved with antigen processing and degradation of small peptides such as angiotensin II (Ang II), vasopressin and oxytocin. We aimed to test for associations between genetic variants in aminopeptidases and HDP. A total of 1282 pregnant women (normotensive controls, n = 693; preeclampsia, n = 342; chronic hypertension with superimposed preeclampsia, n = 61; eclampsia, n = 74; and HELLP syndrome, n = 112) were genotyped for variants in LNPEP (rs27300, rs38034, rs2303138), ERAP1 (rs27044, rs30187) and ERAP2 (rs2549796 rs2927609 rs11135484). We also evaluated the effect of ERAP1 rs30187 on plasma Ang II levels in an additional cohort of 65 pregnant women. The genotype C/C, in ERAP1 rs30187 variant (c.1583 T > C, p.Lys528Arg), was associated with increased risk of eclampsia (OR = 1.85, p = 0.019) whereas ERAP2 haplotype rs2549796(C)-rs2927609(C)-rs11135484(G) was associated with preeclampsia (OR = 1.96, corrected p-value = 0.01). Ang II plasma levels did not differ across rs30187 genotypic groups (p = 0.895). In conclusion, ERAP1 gene is associated with eclampsia whereas ERAP2 is associated with preeclampsia, although the mechanism by which genetic variants in ERAPs influence the risk of preeclampsia and eclampsia remain to be elucidated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Aminopeptidases / genetics*
  • Brazil / epidemiology
  • Eclampsia / diagnosis
  • Eclampsia / epidemiology
  • Eclampsia / genetics*
  • Female
  • Gene Frequency
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genotype
  • HELLP Syndrome / diagnosis
  • HELLP Syndrome / epidemiology
  • HELLP Syndrome / genetics
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Minor Histocompatibility Antigens / genetics*
  • Models, Genetic
  • Odds Ratio
  • Phenotype
  • Population Surveillance
  • Pre-Eclampsia / diagnosis
  • Pre-Eclampsia / epidemiology
  • Pre-Eclampsia / genetics*
  • Pregnancy
  • Reproducibility of Results

Substances

  • Minor Histocompatibility Antigens
  • Aminopeptidases
  • ERAP1 protein, human
  • ERAP2 protein, human