on November 24, 2003
Published online before print November 24, 2003, doi: 10.1161/01.HYP.0000104525.76016.77
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Submitted on July 8, 2003
From Unité de Recherche en Génétique Humaine et Moléculaire and Centre for the Development, Evaluation and Rational Implementation of New Diagnostic Tools (CEDERINDT), Centre de Recherche de l’Hôpital Saint-François d’Assise du CHUQ, and Département de Biologie Médicale, Faculté de Médecine, Université Laval (S.L., C.L., M.-C.R., F.R.), Québec, Canada; and Départment d’Obstetrique Gynécologie, Centre de Recherche Clinique du CHUS, Université de Sherbrooke (J.-M.M.), Sherbrooke, Canada. * To whom correspondence should be addressed. E-mail: Francois.Rousseau{at}crsfa.ulaval.ca.
Abstract--Several association studies of candidate genes for preeclampsia and essential hypertension have led to discordant results, partly because of small sample sizes. Using a large population-based sample of pregnant women, we conducted an association study of 10 polymorphisms in 9 genes and aimed (1) to validate 10 published associations with preeclampsia or essential hypertension, (2) to investigate candidate polymorphisms previously associated with preeclampsia for association with essential hypertension and similarly with polymorphisms previously associated with essential hypertension. From a prospective sample of 3391 nulliparous French Canadian pregnant women, we identified 180 cases of preeclampsia, 203 cases of essential hypertension that were matched with normotensive control subjects (n=310 and 357, respectively). Polymorphisms were genotyped by allele-specific PCR. Among our candidate polymorphisms, the Met allele of Thr174Met of AGT was associated with preeclampsia (P=0.0033). Haplotype analysis revealed that the A-Met-Thr (G1035A-Thr174Met-Met235Thr) haplotype was associated with a 2.1-fold increased risk of preeclampsia (95% CI, 1.4 to 3.4; P=0.0008). In conclusion, we observed a strong association between a specific AGT haplotype and preeclampsia in our population, without replicating previous published associations with either preeclampsia or essential hypertension. Our data support a role for AGT in genetic susceptibility to preeclampsia.
Revised on July 24, 2003
Implication of an AGT Haplotype in a Multigene Association Study With Pregnancy Hypertension
Sébastien Lévesque;
Key words: genetics • polymorphism • haplotypes • hypertension, pregnancy • preeclampsia • population
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