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

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.

Ancient DNA Reveals That the Variability of the DRD4 -521 C/T SNP Associated with Novelty Seeking Behavior is Influenced by Selection in Western South American Populations

“…One study found an association between the T allele of the −521 C/T SNP and increased susceptibility to pre-eclampsia, an illness that would likely be fatal more often at high altitudes where considerable cardiac stress already exists (Korobochka et al 2006). Although the difference was found not to be significant, the much higher proportion of the T allele at higher altitudes (cf.…”