Interactive Effect of the KCNJ11 Ile337Val Polymorphism and Cigarette Smoking on the Antihypertensive Response to Irbesartan in Chinese Hypertensive Patients

OBJECTIVE: This study was designed to detect the association of the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene polymorphism with antihypertensive therapeutic response to irbesartan in a large-scale Chinese hypertensive population. METHODS: A total of 1,099 patients with essential hypertension were enrolled to receive a daily dose of 150mg irbesartan for 27 days. Pretreatment baseline blood pressure (BP) and posttreatment BP on the 28th day were measured. Plasma irbesartan concentrations were measured by high-performance liquid chromatography-fluorescence. The KCNJ11 I337V gene polymorphism was determined using high-throughput TaqMan technology. RESULTS: The HapMap data in the Han Chinese population showed that the I337V was used as a representative for 4 common functional polymorphisms. Our results showed that the association of antihypertensive response to irbesartan and the KCNJ11 genetic variant in the total sample was not significant. However, in nonsmokers, relative to the GG genotype, subjects with the homozygous AA genotype had a significantly higher therapeutic response to irbesartan (adjusted beta ± SE: 4.7±1.9mm Hg, P = 0.015). In smokers, the subjects with the homozygous AA genotype had a significantly lower therapeutic response to irbesartan (adjusted beta ± SE: -5.6±2.5mm Hg, P = 0.026). A multivariate linear regression model confirmed that there was a significant interactive effect between the KCNJ11 gene and smoking on irbesartan treatment (interaction P = 0.001). CONCLUSION The interactive effect of smoking status and the KCNJ11 genotype may influence the antihypertensive effects of irbesartan, which indicates a consideration for future individualized antihypertensive drug treatment.