Single-nucleotide polymorphism associations with preterm delivery: a case-control replication study and meta-analysis
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(Accepted version)
Date
2013
Authors
O'Callaghan, M.
MacLennan, A.
McMichael, G.
Haan, E.
Dekker, G.
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Pediatric Research, 2013; 74(4):433-438
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Michael E. O’Callaghan, Alastair H. MacLennan, Gai L. McMichael, Eric A. Haan and Gustaaf A. Dekker
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Abstract
<h4>Background</h4>The aim of this study was to replicate single-nucleotide polymorphism (SNP) associations with preterm birth (PTB; birth at <37 completed weeks of gestation) and synthesize currently available evidence using meta-analysis.<h4>Methods</h4>Spontaneous PTB cases and controls were selected from an existing cohort. Candidate SNPs were taken from an existing genotype panel. A systematic review was conducted for each SNP in the panel to determine suitability as a PTB candidate. Those with significant associations previously reported in Caucasians were selected for replication. Candidate SNPs were already genotyped in cases and controls and clinical data were accessed from state perinatal and cerebral palsy databases. Association analysis was conducted between each SNP and PTB, and meta-analysis was conducted if there were ≥ 3 studies in the literature. Maternal and fetal SNPs were considered as separate candidates.<h4>Results</h4>A cohort of 170 cases and 583 controls was formed. Eight SNPs from the original panel of genotyped SNPs were selected as PTB candidates and for replication on the basis of systematic literature review results. In our cohort, fetal factor V Leiden (FVL) was significantly associated with PTB (odds ratio (OR): 2.6, 95% confidence interval (CI): 1.31-5.17), and meta-analysis confirmed this association (OR: 2.71, 95% CI: 1.15-6.4).<h4>Conclusion</h4>Replication and meta-analysis support an increased risk of PTB in Caucasians with the fetal FVL mutation.
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Copyright © 2013 International Pediatric Research Foundation, Inc.