A positive association between the human tissue kallikerin gene A2233C polymorphism and blood pressure response to benazepril

ABSTRACT

Background: It is generally believed that essential hypertension is influenced by both genetic and environmental factors, as well as their interactions. Tissue kallikrein encoded by the tissue kallikrein gene (KLK1) is a key serine proteinase of kallikrein–kinin system, which is capable of generating potent vasactive peptides, kinins, by selective cleavage of the kininogen substrate. It was reported that the A2233 → C polymorphism in KLK1 gene is associated with essential hypertension. The aim of this study was to examine whether the molecular variations of KLK1 play role in determining the therapeutic response to benazepril, an ACE inhibitor. Methods: A total of 331 hypertensive individuals were recruited and treated with benazepril for 15 days. A variant impact of KLK1 A2233C was revealed. Chi-square analysis showed that the hypertensive subjects with the mutation genotype (AC + CC) had a higher proportion in systolic blood pressure (SBP, 88.1% vs. 79.0%, χ² = 4.141, p = 0.042) and diastolic blood pressure (DBP, 91.1% vs. 79.2%, χ² = 9.336, p = 0.002), respectively, to benazepril medication in good responders than in poor responders. Logistic regression analysis indicated that the hypertensive subjects with AC + CC genotype were more sensitive to the benazepril therapy in SBP (OR=1.97, 95% CI: 1.02–3.80, p = 0.044) and DBP (OR = 1.91, 95% CI: 2.69–5.16, p = 0.003), as compared with those hypertensive subjects with AA genotype. Conclusion: Our findings suggest that the A2233C polymorphism of KLK1 may be a marker of evaluation of hypertensive subjects’ responses to angiotensin I converting enzyme inhibitors benazepril.

KEYWORDS:

• Angiotensin I converting enzyme inhibitor
• benazepril
• hypertension
• polymorphism
• tissue kallikrein gene

Declaration of interest

The authors declare that they have no conflict of interests.

Funding

This work was supported by the National Natural Science Foundation of China (grant number 81171255 and 81671318) and the Program for Science and Technology Development of Anhui Province (grant number 1501041157).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (grant number 81171255) and the Program for Science and Technology Development of Anhui Province (grant number 1501041157).