摘要：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.
