A Family Based Study of Carbon Monoxide and Nitric Oxide Signalling Genes and Preeclampsia.

Autor: Bauer AE; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA., Avery CL; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.; Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA., Shi M; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA., Weinberg CR; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA., Olshan AF; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA., Harmon QE; Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA., Luo J; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA., Yang J; Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA., Manuck TA; Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina, School of Medicine, Chapel Hill, NC, USA., Wu MC; Biostatistics and Biomathematics Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Williams N; Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK., McGinnis R; Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK., Morgan L; School of Life Sciences, University of Nottingham, Nottingham, UK., Klungsøyr K; Norwegian Institute of Public Health, Oslo, Norway., Trogstad L; Norwegian Institute of Public Health, Oslo, Norway., Magnus P; Norwegian Institute of Public Health, Oslo, Norway., Engel SM; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
Jazyk: angličtina
Zdroj: Paediatric and perinatal epidemiology [Paediatr Perinat Epidemiol] 2018 Jan; Vol. 32 (1), pp. 1-12. Date of Electronic Publication: 2017 Sep 07.
DOI: 10.1111/ppe.12400
Abstrakt: Background: Preeclampsia is thought to originate during placentation, with incomplete remodelling and perfusion of the spiral arteries leading to reduced placental vascular capacity. Nitric oxide (NO) and carbon monoxide (CO) are powerful vasodilators that play a role in the placental vascular system. Although family clustering of preeclampsia has been observed, the existing genetic literature is limited by a failure to consider both mother and child.
Methods: We conducted a nested case-control study within the Norwegian Mother and Child Birth Cohort of 1545 case-pairs and 995 control-pairs from 2540 validated dyads (2011 complete pairs, 529 missing mother or child genotype). We selected 1518 single-nucleotide polymorphisms (SNPs) with minor allele frequency >5% in NO and CO signalling pathways. We used log-linear Poisson regression models and likelihood ratio tests to assess maternal and child effects.
Results: One SNP met criteria for a false discovery rate Q-value <0.05. The child variant, rs12547243 in adenylate cyclase 8 (ADCY8), was associated with an increased risk (relative risk [RR] 1.42, 95% confidence interval [CI] 1.20, 1.69 for AG vs. GG, RR 2.14, 95% CI 1.47, 3.11 for AA vs. GG, Q = 0.03). The maternal variant, rs30593 in PDE1C was associated with a decreased risk for the subtype of preeclampsia accompanied by early delivery (RR 0.45, 95% CI 0.27, 0.75 for TC vs. CC; Q = 0.02). None of the associations were replicated after correction for multiple testing.
Conclusions: This study uses a novel approach to disentangle maternal and child genotypic effects of NO and CO signalling genes on preeclampsia.
(© 2017 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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