Influence of autoantibodies against AT1 receptor and AGTR1 polymorphisms on candesartan-based antihypertensive regimen: Results from the Study of Optimal Treatment in Hypertensive Patients with Anti-AT1-Receptor Autoantibodies trial

Abstract The autoantibodies against angiotensin AT 1 receptors (AT 1 -AAs) in patients with essential hypertension exhibited an agonistic action like angiotensin II and maintained high blood pressure (BP). Angiotensin II receptor gene ( AGTR1 ) polymorphisms were associated with BP response to RAS inhibition in the hypertensive population. Furthermore, the BP response to AT 1 receptor blockers varied significantly among individuals with hypertension. We hypothesized that the polymorphisms of the AGTR1 and AT 1 -AAs might affect antihypertensive response to AT 1 receptor blockers based in patients with primary hypertension. Patients who received a candesartan-based regimen came from the SOT-AT 1 study (Study of Optimal Treatment in Hypertensive Patients with Anti-AT 1 -Receptor Autoantibodies). The established enzyme-labeled immunosorbent assay was used to detect AT 1 -AAs in the sera of the patients. Genotype 3 single nucleotide polymorphisms in AGTR1 gene was used by DNA sequencing. The correlations among AT 1 -AAs, AGTR1 gene polymorphisms or haplotypes, and the antihypertensive effect candesartan-based were analyzed using SPSS. The percentage of systolic BP reduction that was candesartan-based was greater in AT 1 -AA positive groups than in AT 1 -AA negative ones (21 ± 8 vs. 18 ± 9; P  = .001). Meanwhile, systolic BP reduction that was candesartan-based was more significant in the group of rs5186 AC genotypes than AA homozygotes after adjusting for other confounding factors (37.55 ± 13.7 vs. 32.47 ± 17.27 mm Hg; adjusted P  = .028). Furthermore, haplotypes (GCC) and (AAC) had impacts on the antihypertensive effect of candesartan therapy. The AT 1 -AAs, AGTR1 gene polymorphisms and haplotypes solely or jointly have influences on candesartan-based antihypertensive response in patients with primary hypertension.