Haplotypes of the angiotensin II receptor genesAGTR1 andAGTR2 in women with normotensive pregnancy and women with preeclampsia

Abstract

Angiotensin II (AII) acts as a growth factor in local systems, mediating diverse effects such as cellular proliferation and apoptosis. These effects are controlled through two main receptor subtypes: AGTR1 and AGTR2. We studied the haplotype frequencies of both receptor genes in women with preeclamptic pregnancies and normotensive pregnant women. We also looked for any association between AGTR1 genotype at sites in the 5' flanking region and binding of AII to platelets, which express AGTR1, in 58 normotensive pregnant women. There were nine common haplotypes of AGTR1, with no significant difference in haplotype frequency between the two groups of women. Platelet AII binding in normotensive pregnant women was associated with the genotype at g.5245C>T in the 5' flanking region of AGTR1 (GenBank AF245699.1), with CC homozygotes at g.5245 having the lowest levels, and g.5245 TT homozygotes having the highest levels (P=0.05). Two novel polymorphisms were identified in AGTR2 (GenBank AY324607.1) at nucleotides g.1701T>C and g.2184A>T. Variation of AGTR2 could be explained by the existence of four common haplotypes. There was evidence for a significant increase in the frequency of the haplotype TAATGC at nucleotides g.1701, g.2041, g.2184, g.4673, g.4679, and g.4975, respectively (P=0.004), in women with preeclampsia.

Differential expression of angiotensin II type 1 and type 2 receptors at the maternal–fetal interface: potential roles in early placental development

“…Decidua is a significant source of extra-renal Ang II production, and the co-expression of both AGTR1 and AGTR2 by decidual stromal cells suggests auto-and paracrine actions in regulating decidual and placental development and function , Herse et al 2007). Genetic studies have suggested a role for AGTR1 in FGR and pre-eclampsia (Plummer et al 2004, Tower et al 2006. It is tempting to speculate that its transient upregulation in cell columns is a requirement for successful trophoblast invasion, and that its failure may play a role in the pathogenesis of pregnancy complications.…”

“…Despite evidence suggesting a role for both the receptors in the origins of pre-eclampsia and FGR (Plummer et al 2004, Tower et al 2006, Xia et al 2007, comprehensive localisation studies of the AGTR1 and AGTR2 receptors in human placental EVT populations during early pregnancy have not been conducted. Interactions between AGTR1 and AGTR2 have been previously described, through the formation of heterodimers (AbdAlla et al 2001) and the interaction between the two receptors in other tissues is antagonistic in terms of both opposing function and cellular signalling (Dinh et al 2001).…”

Post-Transcriptional Control of Angiotensin II Type 1 Receptor Regulates Osteosarcoma Cell Death

“…Cellular apoptosis is regulated by certain proteins, which are apoptosis activating proteins, e.g. Bid, Bak, Bad, and angiotensin II type 1 receptor (AGTR1) [14, 15]. …”

Angiotensin II type 2 receptor gene polymorphisms in cardiovascular disease

“…Recent haplotype analysis of the AT 2 receptor gene has revealed that four common haplotypes account for over 90% of the haplotypes present in a Caucasian population. 8 Furthermore, the -1332G/A and 3123C/A polymorphisms are in high linkage disequilibrium.…”