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Mol. Hum. Reprod. Advance Access published online on February 2, 2006
Molecular Human Reproduction, doi:10.1093/molehr/gal004
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received October 13, 2005
Revised December 9, 2005
Accepted December 13, 2005

Article

Association between a functional dopamine D4 receptor promoter region polymorphism (-C521T) and pre-eclampsia: a family-based study

Roman Korobochka 1 *, Inga Gritsenko 2, Ron Gonen 1, Richard P. Ebstein 2, and Gonen Ohel 1

1 Department of Obstetrics and Gynecology, Bnai Zion Medical Center, Technion, Haifa, Israel
2 Psychology Department, Scheinfeld Center of Human Genetics for the Social Sciences, Hebrew University, Jerusalem, Israel; S. Herzog Memorial Hospital, Jerusalem, Israel

* To whom correspondence should be addressed.
Roman Korobochka, E-mail: roman.korobochka{at}b-zion.org.il


  Abstract

Although many candidate genes have been studied in pre-eclampsia (PE), the important class of catecholamine receptors that contribute to sympathetic tone and blood pressure regulation has yet to be investigated. We therefore examined the dopamine D4 receptor (DRD4) gene. We performed a prospective family-based study in 50 families (patient and both her parents) who were genotyped for three DRD4 promoter regions. These single-nucleotide polymorphisms (SNPs) were tested for association using family-based association test (FBAT) that also included two quantitative measures, aspartate aminotransferase [serum glutamic oxalacetic transaminase (SGOT)] and systolic blood pressure. SNPs were assayed using a commercially available SNAPSHOT kit and PCR products were analysed in an ABI 310 DNA analyser. A significant association (preferential transmission of the T allele from a heterozygous parent to affected mother) was observed between the -C521T SNP and PE (P = 0.019). Significant association was also observed between the -521T allele and two-dimensional measures of PE : GOT (P = 0.039) and systolic blood pressure (P = 0.036). The DRD4 promoter region -C521T SNP that reduces transcriptional efficiency of this gene is suggested to contribute to developing PE. Additionally, DRD4 -521 TT homozygosity may be a marker for severe PE.

Keywords: dopamine D4 receptor/family study/polymorphism/pre-eclampsia.
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