Interactive effect of angiotensin II type 1 receptor (AGT1R) polymorphisms and plasma irbesartan concentration on antihypertensive therapeutic responses to irbesartan

Jiang, Shanqun; Hsu, Yi Hsiang; Venners, Scott A.; Zhang, Yan; Huang, Xing; Wang, Xiaobin; Xu, Xiping

doi:10.1097/hjh.0b013e32834494f6

Cited by 14 publications

(10 citation statements)

References 32 publications

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“…This would suggest increased risk of arrhythmias; however, we did not find an association between rs5186 and SCD in the current population [16]. In patients with at least one copy of the C allele in AGTR1, there is a more pronounced decrease in blood pressure in response to angiotensin receptor blockers [17,18] but not angiotensin-converting enzyme inhibitors [19]. Our results demonstrate a higher likelihood of adverse events with the C allele, which at first seems counterintuitive.…”

Section: Discussioncontrasting

confidence: 70%

Angiotensin-related genetic determinants of cardiovascular disease in patients undergoing hemodialysis

Moe

Long

Schwantes-An

et al. 2018

Nephrology Dialysis Transplantation

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Section: Discussioncontrasting

confidence: 70%

Angiotensin-related genetic determinants of cardiovascular disease in patients undergoing hemodialysis

Moe

Long

Schwantes-An

et al. 2018

Nephrology Dialysis Transplantation

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“…The effective control of hypertension to reduce the morbidity and mortality of cardiovascular diseases is a global goal [ 25 ]. Interindividual variation in the BP response to the commonly used antihypertensive drug ARB is attributed to environmental and genetic factors, such as the polymorphisms in the genes involving targeted receptor and drug metabolism [ 14 , 26 , 27 ]. In the present study, we analyzed the association of polymorphisms AGTR1 A1166C and CYP2C9 ∗3 with the antihypertensive effect of valsartan based on real-world data.…”

Section: Discussionmentioning

confidence: 99%

“…Dong et al also observed an enhanced antihypertensive effect of irbesartan only in male patients with AC and CC genotypes of AGTR1 A1166C [ 33 ]. In another study on a large Chinese cohort ( n = 1049), the decrease in BP was positively correlated with irbesartan concentration in the carriers with the C allele of AGTR1 A1166C, suggesting an impact of the interaction of AGTR1 polymorphism and irbesartan concentration on the antihypertensive response to irbesartan [ 27 ]. Conversely, the AGTR1 1166 C allele was not linked to the irbesartan concentration-BP response correlation in a Swedish study ( n = 42).…”

Section: Discussionmentioning

confidence: 99%

Association of AGTR1 A1166C and CYP2C9∗3 Gene Polymorphisms with the Antihypertensive Effect of Valsartan

Liu

Kong

Jiang

et al. 2022

International Journal of Hypertension

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Background. The differences in the antihypertensive treatment with angiotensin type II receptor blockers (ARBs) may be attributed to polymorphisms in genes involving drug-targeted receptor and drug metabolism. The present study aimed to investigate whether the antihypertensive effect of the ARB drug valsartan was associated with angiotensin II type 1 receptor (AGTR1) gene polymorphism (A1166 C) and cytochrome P450 enzyme 2C9 (CYP2C9) gene polymorphism (CYP2C9∗3). Methods. 281 patients with hypertension who received valsartan monotherapy in the past month were included in this retrospective study. Polymerase chain reaction-melting curve analysis was performed to genotype the AGTR1 and CYP2C9 gene polymorphisms. Based on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the time of visit, the patients were divided into well-controlled group (n = 144, SBP/DBP <140/90 mmHg) and poorly controlled group (n = 137, SBP/DBP ≥140/90 mmHg). Results. Older age, decreased history of drinking, a higher proportion of mild-to-moderate hypertension, lower alanine aminotransferase levels, and higher high-density lipoprotein cholesterol levels were observed in the well-controlled group than the poorly controlled group. Higher frequencies of the C allele and AC + CC genotype of AGTR1 A1166C were detected in the well-controlled than the poorly controlled patients ( P = 0.005 and P = 0.006). After adjustment for demographic and environmental factors, the CC + AC genotype of AGTR1 A1166C was markedly linked to better hypertension control with valsartan treatment compared to the AA genotype (odds ratio: 2.836, 95% confidence interval: 1.199–6.705, P = 0.018). No significant difference was observed in the allele or genotype distribution of CYP2C9∗3 polymorphism between well-controlled and poorly controlled patients. Conclusions. The current data suggested that the AGTR1 A1166 C polymorphism may be associated with the antihypertensive effect of valsartan, and carriers with AC and CC genotypes may have a better antihypertensive efficacy response to valsartan treatment.

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“…Actually, for the treatment of hypertensive patients, it is still obscure what is a determinant factor in each individual patient's response to irbesartan treatment. Nevertheless, growing evidence suggests that gene polymorphism in drug-targeted receptors or metabolizers is related to distinct response to antihypertensive drugs like irbesartan [12], which implies that it is necessary to identify the correlation between gene polymorphism in particular patients and irbesartan therapeutic efects [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Influence of AGTR1 and ABCB1 Gene Polymorphism on the Curative Effect of Irbesartan

Wang

You

et al. 2022

International Journal of Hypertension

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The interindividual heterogeneity in response to the antihypertensive effect of irbesartan has received considerable attention because of gene polymorphism. In this study, we investigated the new combinational influences of AGTR1 and ABCB1 gene polymorphism on the therapeutic effect of irbesartan among Chinese hypertensive patients. A total of 353 samples including 168 normal people and 185 hypertensive patients were adopted, and genotypes comprise ABCB1 (CC, CT, and TT) and AGTR1 (AA and AC) in this study. The results of multiple linear regression models showed that no statistically significant differences were observed in blood pressure change following irbesartan administration in each genotype from either ABCB1 (CC, CT, and TT) or AGTR1 (AA and AC). However, spline smoothing analysis demonstrated that the blood pressure therapeutic responses of irbesartan presented a noticeable difference among different ABCB1 genotypes when irbesartan doses reached over 300 ng/mL. Eventually, we assumed that the different drug responses of irbesartan among various AGTR1 genotypes were due to the diversity of the irbesartan-conjugated protein, which is responsible for crossing-coupled intracellular G-protein-coupled receptors (GPCRs).

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Interactive effect of angiotensin II type 1 receptor (AGT1R) polymorphisms and plasma irbesartan concentration on antihypertensive therapeutic responses to irbesartan

Abstract: Our data suggest that AGT1R gene polymorphisms and plasma concentration of irbesartan can act interactively to modulate individual response to antihypertensive therapy using irbesartan.

Cited by 14 publications

References 32 publications

Angiotensin-related genetic determinants of cardiovascular disease in patients undergoing hemodialysis

Angiotensin-related genetic determinants of cardiovascular disease in patients undergoing hemodialysis

Association of AGTR1 A1166C and CYP2C9∗3 Gene Polymorphisms with the Antihypertensive Effect of Valsartan

Influence of AGTR1 and ABCB1 Gene Polymorphism on the Curative Effect of Irbesartan

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