A1166C variant of angiotensin II type 1 receptor gene is associated with severe hypertension in pregnancy independently of T235 variant of angiotensinogen gene

Hypertension in pregnancy (HP) is a multifactorial disease manifested due to a complex combination of environmental factors and several predisposing genes including factors in the renin angiotensin system. The aim of this study was to assess the association between the A1166C variant of the angiotensin II type 1 receptor (AT1) gene and severe HP. We carried out association studies and multivariate analyses including other candidate causal factors of HP such as the M235T variant of the angiotensinogen (AGT) gene, prepregnancy body mass index (BMI), and family history of hypertension in Japanese subjects. One hundred and fourteen patients with severe HP and 291 normal pregnancy controls were genotyped. Among primiparous subjects, the frequency of "AC+CC genotype of AT1" was significantly higher in severe HP than in the controls. A multivariate analysis with "AC+CC genotype of AT1" and "TT genotype of AGT" revealed that these were independently associated with primiparous severe HP. However, when "family history of hypertension" and "prepregnancy BMI greater than or equal to25" were added as factors examined in the multivariate analysis, only "TT genotype of AGT" and "family history of hypertension" were found to be independent potent factors. The present results suggest that the C1166 allele of the AT1 gene may be concerned with the predisposition to essential hypertension independently of the T235 allele of the AGT gene.