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Association between maternal micronutrient status, oxidative stress, and common genetic variants in antioxidant enzymes at 15 weeks' gestation in nulliparous women who subsequently develop preeclampsia

Lookup NU author(s): Professor John Hesketh, Dr Catherine Meplan



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Preeclampsia is a pregnancy-specific condition affecting 2-7% of women and a leading cause of perinatal and maternal morbidity and mortality. Deficiencies of specific micronutrient antioxidant activities associated with copper, selenium, zinc, and manganese have previously been linked to preeclampsia at the time of disease. Our aims were to investigate whether maternal plasma micronutrient concentrations and related antioxidant enzyme activities are altered before preeclampsia onset and to examine the dependence on genetic variations in these antioxidant enzymes. Predisease plasma samples (15 +/- 1 weeks' gestation) were obtained from women enrolled in the international Screening for Pregnancy Endpoints (SCOPE) study who subsequently developed preeclampsia (n = 244) and from age- and BMI-matched normotensive controls (n = 472). Micronutrient concentrations were measured by inductively coupled plasma mass spectrometry; associated antioxidant enzyme activities, selenoprotein-P, ceruloplasmin concentration and activity, antioxidant capacity, and markers of oxidative stress were measured by colorimetric assays. Sixty-four tag single-nucleotide polymorphisms (SNPs) within genes encoding the antioxidant enzymes and selenoprotein-P were genotyped using allele-specific competitive PCR. Plasma copper and ceruloplasmin concentrations were modestly but significantly elevated in women who subsequently developed preeclampsia (both P < 0.001) compared to controls (median (IQR), copper, 1957.4 (1787, 2177.5) vs 1850.0 (1663.5, 2051.5) mu g/L; ceruloplasmin, 2.5 (1.4, 3.2) vs 2.2 (1.2, 3.0) mu g/ml). There were no differences in other micronutrients or enzymes between groups. No relationship was observed between genotype for SNPs and antioxidant enzyme activity. This analysis of a prospective cohort study reports maternal micronutrient concentrations in combination with associated antioxidant enzymes and SNPs in their encoding genes in women at 15 weeks' gestation that subsequently developed preeclampsia. The modest elevation in copper may contribute to oxidative stress, later in pregnancy, in those women that go on to develop preeclampsia. The lack of evidence to support the hypothesis that functional SNPs influence antioxidant enzyme activity in pregnant women argues against a role for these genes in the etiology of preeclampsia. (C) 2014 The Authors. Published by Elsevier Inc.

Publication metadata

Author(s): Mistry HD, Gill CA, Kurlak LO, Seed PT, Hesketh JE, Meplan C, Schomburg L, Chappell LC, Morgan L, Poston L, SCOPE Consortium

Publication type: Article

Publication status: Published

Journal: Free Radical Biology and Medicine

Year: 2015

Volume: 78

Pages: 147-155

Print publication date: 01/01/2015

Online publication date: 06/11/2014

Acceptance date: 29/10/2014

Date deposited: 02/04/2015

ISSN (print): 0891-5849

ISSN (electronic): 1873-4596

Publisher: Elsevier Inc.


DOI: 10.1016/j.freeradbiomed.2014.10.580


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Funder referenceFunder name
1060508Tommy's Charity, UK
PG/11/22/28800British Heart Foundation
SCO39280Tommy's Charity, UK