Genetics of preeclampsia: what are the challenges?
Despite recent efforts to identify susceptibility genes of preeclampsia, the genetic determinants of the condition remain ill-defined, as is the situation for most disorders of complex inheritance patterns. The angiotensinogen, factor V, and methylenetetrahydrofolate reductase genes have been investigated in different populations, as have other genes involved in blood pressure, vascular volume control, thrombophilia, lipid metabolism, oxidative stress, and endothelial dysfunction. The study of the genetics of complex traits is faced with both methodological and genetic issues; these include adequate sample size to allow for the identification of modest genetic effects, of gene-gene and gene-environment interactions, the study of adequate quantitative traits and extreme phenotypes, haplotype analyses, statistical genetics, genome-wide (hypothesis-free) versus candidate-gene (hypothesis-driven) approaches, and the validation of positive associations. The use of genetically well-characterized populations showing a founder effect, such as the French-Canadian population of Quebec, in genetic association studies, may help to unravel the susceptibility genes of disorders showing complex inheritance, such as preeclampsia. It is necessary to better evaluate the role of the fetal genome in the resulting predisposition to preeclampsia and its complications. Eventually, we may be able to integrate genetic information to better identify the women at risk of developing preeclampsia, and to improve the management of those suffering from this condition.
Bernard
Nathalie
N
Unité de recherche en périnatalogie, Centre de recherche, Hôpital Saint-François d'Assise, Centre hospitalier universitaire de Québec, Québec, QC, Canada.
Giguère
Yves
Y
D000328:Adult; D000808:Angiotensinogen / Q000235:genetics; D005165:Factor V / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D011225:Pre-Eclampsia / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control; D011247:Pregnancy
D000808:Angiotensinogen; D005165:Factor V; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)