ClinVar

Variants in the human AGTR1A gene may affect blood pressure. Bonnardeaux et al. (1994) identified an association between several AGTR1A gene polymorphisms and hypertension (145500). Specifically, an A-to-C variant in the 3-prime UTR at nucleotide 1166 (cDNA numbering from the ATG start codon) showed a significantly elevated frequency in 206 Caucasian patients with essential hypertension. Wang et al. (1997) did a case-control study of the 1166A-C variant in 108 Caucasian hypertensive patients with a strong family history (2 affected parents) and early onset disease. The frequency of the 1166C allele was 0.40 in hypertensives and 0.29 in normotensives.

Kobashi et al. (2004) genotyped 114 Japanese patients with severe hypertension in pregnancy (HP) and 291 normal pregnancy controls. Among primiparous patients, the frequency of the AC and CC genotypes at nucleotide 1166 of the AGTR1 gene was significantly higher in severe HP than in the controls. A multivariate analysis with the AC and CC genotypes at nucleotide 1166 of the AGTR1 gene and TT genotype at codon 235 of the AGT gene (106150.0001) revealed that these were independently associated with primiparous severe HP.

Animal miRNAs regulate gene expression through base pairing to their targets within the 3-prime untranslated region (UTR) of protein-coding genes. Single-nucleotide polymorphisms (SNPs) located within such target sites can affect miRNA regulation. Sethupathy et al. (2007) mapped annotated SNPs onto a collection of experimentally supported human miRNA targets. Of the 143 experimentally supported human target sites, 9 contained 12 SNPs. They further experimentally investigated one of these target sites for miR155 (see 609337), that within the 3-prime UTR of the human AGTR1 gene, which contains SNP rs5186. Using reporter silencing assays, they showed that miR155 downregulates the expression only of the 1166A, and not the 1166C, allele of rs5186. Since the 1166C allele has been associated with hypertension in many studies, the 1166C allele may be functionally associated with hypertension by abrogating regulation by miR155, thereby elevating AGTR1 levels. Since miR155 is on chromosome 21, Sethupathy et al. (2007) hypothesized that the observed lower blood pressure in trisomy 21 is partially caused by the overexpression of miR155 leading to allele-specific underexpression of AGTR1. Indeed, they showed in fibroblasts from monozygotic twins discordant for trisomy 21 that levels of AGTR1 protein are lower in trisomy 21.