Disentangling Fetal and Maternal Susceptibility for Pre-Eclampsia: A British Multicenter Candidate-Gene Study

FONTE

American Society of Human Genetics

RESUMO

The Genetics of Pre-Eclampsia (GOPEC) collaboration aims to identify genetic factors in U.K. families affected by pre-eclampsia. A number of genetic studies have reported associations with pre-eclampsia, but attempts to replicate these findings have yielded inconsistent results. We describe the results of extensive genotyping of seven candidate genes previously reported as conferring susceptibility to pre-eclampsia. Six hundred fifty-seven women affected by pre-eclampsia and their families were genotyped at 28 single-nucleotide polymorphisms in the genes encoding angiotensinogen, the angiotensin receptors, factor V Leiden variant, methylene tetrahydrofolate reductase, nitric oxide synthase, and TNFα. Genotypes were analyzed by the transmission/disequilibrium test. Genotype risk ratios (GRRs) associated with maternal genotypes had a range of 0.70–1.16; GRRs associated with fetal genotypes had a range of 0.72–1.11. No GRR achieved the prespecified criteria for statistical significance (posterior probability >.05). We conclude that none of the genetic variants tested in this large study of strictly defined pre-eclamptic pregnancies confers a high risk of disease. The results emphasize the importance of conducting rigorously designed studies of adequate size to provide precise genetic risks with narrow confidence intervals, if overreporting of false-positive results is to be avoided.

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