Pre-eclampsia and its related syndromes are significant causes of maternal and fetal death, but much remains unclear about the underlying disease mechanisms. Epidemiological research has consistently demonstrated a familial predisposition to pre-eclampsia, which has encouraged genetic research in this area. The goal is the discovery of susceptibility genes which will inform understanding of the pathophysiology of pre-eclampsia, and may prove to be targets for therapeutic or preventative strategies. This review examines the application of molecular technologies to the search for genetic clues in pre-eclampsia and emphasizes the importance of integrative approaches. The results of recent genome-wide linkage studies have been particularly encouraging, identifying a number of loci which merit closer examination. Candidate gene studies have proved less fruitful, generating conflicting and inconclusive results. Possible explanations and remedies for this deficiency are discussed with a view to stimulating closer collaboration between researchers in this field.

1. We investigated whether abnormalities of gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (7–36 amide) (GLP-1) contribute to the hypertriglyceridaemia and hyperinsulinaemia in hypertriglyceridaemic subjects. Serum triglycerides and plasma glucose GIP, GLP-1 and immunoreactive insulin (IRI) concentrations were measured before and after a mixed meal in 15 hypertriglyceridaemic patients and in eight healthy normotriglyceridaemic control subjects. 2. Integrated post-prandial GIP concentrations were greater than in controls ( P < 0.05) and correlated positively with both fasting and integrated post-prandial triglyceride concentrations ( P < 0.05 for both). Fasting and integrated post-prandial IRI levels were higher in hypertriglyceridaemic subjects than in controls ( P < 0.02 and P < 0.05 respectively) and correlated positively with fasting triglycerides ( P < 0.02 and P < 0.001 respectively) and integrated post-prandial triglycerides ( P < 0.005 and P < 0.05 respectively). There was no correlation between GIP concentrations and either fasting or post-prandial IRI levels. Fasting and post-prandial concentrations of GLP-1 were similar in patients and controls. 3. Hypertriglyceridaemic subjects have post-prandial hyperGIPaemia in addition to the well-documented hyperinsulinaemia. We found no association between GIP and insulin. There is, however, clear evidence for an association between post-prandial GIP concentrations and triglyceride levels. We suggest that this association may depend on changes in lipoprotein lipase activity and that there may be a feedback loop between GIP and triglyceride lipolysis.