Scholarlink

<p>Considerable inter-individual variability has been observed in the blood pressure response to valsartan/hydrochlorothiazide (Valsartan/HCTZ), and genetic differences within the renin–angiotensin system may contribute to this heterogeneity. This prospective cohort study included 354 hypertensive patients treated with Valsartan/HCTZ (80/12.5&#xa0;mg or 160/12.5&#xa0;mg). Baseline and 4-week BP measurements were recorded following standardized procedures, and five variants (<i>AGT</i> rs5050, rs5051, rs699, rs4762, and <i>ACE</i> I/D) were genotyped using PCR-based methods. Associations were evaluated through linear and multivariate regression, and multilocus interactions were examined using estimated marginal means. Overall, the cohort showed reductions of 23.2 ± 16.4 mmHg in SBP and 14.8 ± 10.9 mmHg in DBP. Among clinical factors, normal BMI was associated with greater reductions (22.9 ± 15.9; 15.5 ± 9.3 mmHg) compared with BMI ≥ 35&#xa0;kg/m² (14.2 ± 17.3; 10.7 ± 11.4 mmHg). Hypertension-specific diets produced larger SBP decreases (25.6 ± 17.6 mmHg) than unrestricted diets (22.9 ± 16.3 mmHg). Increasing dose had only a modest additional effect. <i>AGT</i> rs5050 showed the strongest genetic association, with SBP decreasing by 26 mmHg in CA/CC carriers versus 13.4 mmHg in AA (<i>p</i> &lt; 0.001). <i>ACE</i> I/D significantly affected DBP, with II carriers achieving 13.7 mmHg versus 8.0 mmHg in DD (<i>p</i> = 0.017). A significant <i>AGT</i> rs5050 × <i>ACE</i> I/D interaction revealed the greatest reduction in AC/II (20.6 ± 2.3 mmHg) and the lowest in AA/DD (3.80 ± 2.33 mmHg). These findings highlight meaningful multilocus effects and support the potential for genotype-guided antihypertensive therapy.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Pharmacogenetics of RAS-affecting AGT and ACE variants and the efficacy of Valsartan/HCTZ therapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月7日

查看全文
  • Alija Baig,
  • Syed Muhammad Mukarram Shah,
  • Abdulrahman Saad Alfaiz,
  • Muath A. Alammar,
  • Mohammad Dhuwayhi Ghazi Alotaibi,
  • Abdur Rauf,
  • Aiman Begum,
  • Zia Ul Hassan,
  • Noorulain Ainy,
  • Wahby Mohammed Babaresh,
  • Zakiullah

摘要

Considerable inter-individual variability has been observed in the blood pressure response to valsartan/hydrochlorothiazide (Valsartan/HCTZ), and genetic differences within the renin–angiotensin system may contribute to this heterogeneity. This prospective cohort study included 354 hypertensive patients treated with Valsartan/HCTZ (80/12.5 mg or 160/12.5 mg). Baseline and 4-week BP measurements were recorded following standardized procedures, and five variants (AGT rs5050, rs5051, rs699, rs4762, and ACE I/D) were genotyped using PCR-based methods. Associations were evaluated through linear and multivariate regression, and multilocus interactions were examined using estimated marginal means. Overall, the cohort showed reductions of 23.2 ± 16.4 mmHg in SBP and 14.8 ± 10.9 mmHg in DBP. Among clinical factors, normal BMI was associated with greater reductions (22.9 ± 15.9; 15.5 ± 9.3 mmHg) compared with BMI ≥ 35 kg/m² (14.2 ± 17.3; 10.7 ± 11.4 mmHg). Hypertension-specific diets produced larger SBP decreases (25.6 ± 17.6 mmHg) than unrestricted diets (22.9 ± 16.3 mmHg). Increasing dose had only a modest additional effect. AGT rs5050 showed the strongest genetic association, with SBP decreasing by 26 mmHg in CA/CC carriers versus 13.4 mmHg in AA (p < 0.001). ACE I/D significantly affected DBP, with II carriers achieving 13.7 mmHg versus 8.0 mmHg in DD (p = 0.017). A significant AGT rs5050 × ACE I/D interaction revealed the greatest reduction in AC/II (20.6 ± 2.3 mmHg) and the lowest in AA/DD (3.80 ± 2.33 mmHg). These findings highlight meaningful multilocus effects and support the potential for genotype-guided antihypertensive therapy.