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Disease Markers
Volume 31, Issue 2, Pages 83-89
http://dx.doi.org/10.3233/DMA-2011-0804

Endothelial Nitric Oxide Synthase Haplotypes Are Associated with Preeclampsia in Maya Mestizo Women

Lizbeth Díaz-Olguín,1 Ramón Mauricio Coral-Vázquez,2 Thelma Canto-Cetina,3 Samuel Canizales-Quinteros,4 Belem Ramírez Regalado,1 Genny Fernández,5 and Patricia Canto1

1División de Investigación Biomédica, Subdirección de Enseñanza e Investigación, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, México, D.F., Mexico
2Sección de Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, D.F., & División de Medicina Genómica, Centro Médico Nacional "20 de Noviembre", Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, México, D.F., Mexico
3Laboratorio de Biología de la Reproducción, Departamento de Salud Reproductiva y Genética, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Mérida Yucatán, Mexico
4Facultad de Química, Universidad Nacional Autónoma de México, México, D.F., México, Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, México, D.F., Mexico
5Servicio Prenatal del Hospital Materno Infantil, S.S., Mérida, Yucatán, Mexico

Received 31 August 2011; Accepted 31 August 2011

Copyright © 2011 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Preeclampsia is a specific disease of pregnancy and believed to have a genetic component. The aim of this study was to investigate if three polymorphisms in eNOS or their haplotypes are associated with preeclampsia in Maya mestizo women.

A case-control study was performed where 127 preeclamptic patients and 263 controls were included. Genotyped and haplotypes for the -768T→C, intron 4 variants, Glu298Asp of eNOS were determined by PCR and real-time PCR allelic discrimination. Logistic regression analysis with adjustment for age and body mass index (BMI) was used to test for associations between genotype and preeclampsia under recessive, codominant and dominant models. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r2, and haplotype analysis was conducted.

Women homozygous for the Asp298 allele showed an association of preeclampsia. In addition, analysis of the haplotype frequencies revealed that the -786C-4b-Asp298 haplotype was significantly more frequent in preeclamptic patients than in controls (0.143 vs. 0.041, respectively; OR = 3.01; 95% CI = 1.74–5.23; P = 2.9 × 10−4).

Despite the Asp298 genotype in a recessive model associated with the presence of preeclampsia in Maya mestizo women, we believe that in this population the -786C-4b-Asp298 haplotype is a better genetic marker.