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(Hypertension. 2004;44:702.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Endothelial NO Synthase Genotype and Risk of Preeclampsia

A Multicenter Case-Control Study

Norma C. Serrano; Juan P. Casas; Luis A. Díaz; Carolina Páez; Clara M. Mesa; Rodrigo Cifuentes; Alvaro Monterrosa; Alejandro Bautista; Emma Hawe; Aroon D. Hingorani; Patrick Vallance; Patricio López-Jaramillo

From the Universidad Autónoma de Bucaramanga (N.C.S., L.A.D., C.P.), Colombia; Centre for Clinical Pharmacology (J.P.C., A.D.H., P.V.), Department of Medicine, BHF Laboratories at University College London (UCL), United Kingdom; Instituto de Ciencias de la Salud, Colombia (C.M.M.); Universidad del Valle (R.C.), Colombia; Universidad de Cartagena, Colombia (A.M.); Universidad Nacional de Colombia (A.B.), Colombia; Centre for Cardiovascular Genetics (E.H.), Department of Medicine, British Heart Foundation Laboratories at UCL; Instituto Colombiano de Investigaciones Biomédicas (P.L.-J.), Colombia; and Fundación Cardiovascular del Oriente Colombiano, Colombia (P.L.-J.).

Correspondence to Dr Norma C. Serrano, Genetics and Human Biology Laboratory, Department of Medicine at Universidad Autónoma de Bucaramanga, Colombia, Campus el Bosque, Calle 157 No. 19-55 Cañaveral Parque, Colombia. E-mail nserrano{at}unab.edu.co

Polymorphisms in the endothelial NO synthase (eNOS) gene have been evaluated as risk factors for preeclampsia. However, data from small studies are conflicting. We assessed whether eNOS genotypes alter the risk of preeclampsia in a population in which the incidence of this disorder is high. A total of 844 young pregnant women (322 preeclamptic and 522 controls) were recruited from 5 cities. Genotyping for the Glu298Asp, intron-4 and –786TC polymorphisms in the eNOS gene was conducted. Multivariate odds ratios (ORs) were obtained to estimate the association of individual polymorphisms and haplotypes with preeclampsia risk. No increase in the risk of preeclampsia for the intron-4 or –786TC polymorphisms was observed under any model of inheritance. In contrast, in women homozygous for the Asp298 allele, the adjusted OR for preeclampsia was 4.60 (95% confidence interval [CI], 1.73 to 12.22) compared with carriers of the Glu298 allele. After a multivariate analysis, carriage of the "Asp298–786C-4b" haplotype was also associated with increased risk of preeclampsia (OR, 2.11 [95% CI, 1.33 to 3.34]) compared with carriers of the "Glu298–786T-4b" haplotype. The eNOS Glu298Asp polymorphism and the Asp298–786C-4b haplotype are risk factors for preeclampsia.

Key Words: preeclampsia • nitric oxide synthase • polymorphism • haplotypes • case-control studies

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