title: 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 AT1 receptors (AT1-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 AT1 receptor blockers varied significantly among individuals with hypertension. We hypothesized that the polymorphisms of the AGTR1 and AT1-AAs might affect antihypertensive response to AT1 receptor blockers based in patients with primary hypertension. Patients who received a candesartan-based regimen came from the SOT-AT1 study (Study of Optimal Treatment in Hypertensive Patients with Anti-AT1-Receptor Autoantibodies). The established enzyme-labeled immunosorbent assay was used to detect AT1-AAs in the sera of the patients. Genotype 3 single nucleotide polymorphisms in AGTR1 gene was used by DNA sequencing. The correlations among AT1-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 AT1-AA positive groups than in AT1-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 AT1-AAs, AGTR1 gene polymorphisms and haplotypes solely or jointly have influences on candesartan-based antihypertensive response in patients with primary hypertension.
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China; Department of Cardiovascular Medicine, Zhongshan Hospital, Sun Yat-sen University, Guangdong 528400, People's Republic of China. Electronic address: syx1298509@163.com.
authors.forename: Yanxiang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Cardiovascular Medicine, Zhongshan Hospital, Sun Yat-sen University, Guangdong 528400, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Cardiovascular Medicine, Zhongshan Hospital, Sun Yat-sen University, Guangdong 528400, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Cardiovascular Medicine, Zhongshan Hospital, Sun Yat-sen University, Guangdong 528400, People's Republic of China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Ma
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China. Electronic address: redpeak8848@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000276:immunology*; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: C544065:AGTR1 protein, human; D047228:Angiotensin II Type 1 Receptor Blockers; D001323:Autoantibodies; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C081643:candesartan
keywords: Hypertension; angiotensin-receptor blockers; autoantibodies; polymorphism