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

Autor: Priya Duggal, Carlos E. M. Gomes, Amanda Samara Davi de Lima, Leonardo Capistrano Ferreira, Selma M. B. Jeronimo, Paulo Ricardo Porfírio do Nascimento, Ingrid De Paula Holanda
Rok vydání: 2021
Předmět:
0301 basic medicine
Aminopeptidases
Linkage Disequilibrium
0302 clinical medicine
Gene Frequency
Pre-Eclampsia
Pregnancy
Genetics research
Genotype
Odds Ratio
Eclampsia
030212 general & internal medicine
reproductive and urinary physiology
Multidisciplinary
female genital diseases and pregnancy complications
Phenotype
Population Surveillance
Hypertension
Medicine
Female
Brazil
HELLP Syndrome
medicine.medical_specialty
HELLP syndrome
Science
Article
Preeclampsia
Minor Histocompatibility Antigens
03 medical and health sciences
Internal medicine
medicine
Humans
Genetic Predisposition to Disease
Alleles
Genetic Association Studies
Genetic association study
Genetic association
Models
Genetic
business.industry
Haplotype
Reproducibility of Results
medicine.disease
Angiotensin II
030104 developmental biology
Endocrinology
Haplotypes
business
Zdroj: Scientific Reports
Scientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
ISSN: 2045-2322
1113-5484
DOI: 10.1038/s41598-021-86240-z
Popis: 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.
Databáze: OpenAIRE
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