Haplotypes of the angiotensin II receptor genes AGTR1 and AGTR2 in women with normotensive pregnancy and women with preeclampsia

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. Hum Mutat 24:14–20, 2004. © 2004 Wiley‐Liss, Inc.