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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.

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