Abstract 2404: Polymorphisms of Regulator of G-Protein Signaling 2 Gene Affect the Antihypertensive Efficiency of Angiotensin Receptor Blocker
Objective: The efficiency of antihypertensive drugs varies in patients with high blood pressure, and is considered to be influenced by individual genetic backgrounds. Recent study reveals the important role of the regulator of G-protein signaling 2 (RGS2) in cardiovascular regulation. This study was performed to analyze the influence of RGS2 gene polymorphism to the effectiveness of antihypertensive agents including angiotensin receptor blocker (ARB), angiotensin conveting enzyme inhibitor (ACEI), β-blocker and calcium channel blocker (CCB).
Methods: We evaluated averaged blood pressure (BP) of essential hypertension (EHT) patients, measured on three consecutive outpatient clinic visits, before and after taking ARB(n=75), ACEI(n=95), β-blocker(n=107) and CCB(n=199). We performed direct sequencing for SNPs hunting and analyzed 11 SNPs of RGS2 using TaqMan PCR method.
Results: Systolic (S) and Diastolic (D) BP were significantly lowered after antihypertensive treatment. There were significant differences of delta-BP (BP post - BP pre) between the genotypes of 2 SNPs only in female subjects taking ARB (n=35) (RGS2 1891–1892del TC; delta-DBP II (n= 11) −0.3±4.7mmHg vs. ID+DD (n=23) −5.2±5.8mmHg p=0.02, RGS2 1026T>A; delta-DBP TT (n=11) −0.3±4.7mmHg vs. TA+AA (n=22) −5.2±6.0mmHg, p=0.02).These 2 SNPs of RGS2 showed tightly linkage disequilibrium. There were not significant differences of delta-BP between the genotypes of patients taking other three drugs. The genetic background of RGS2 influenced only the efficacy of ARB, and did not affect those of ACEI, β-blocker and CCB.
Conclusions: The 2 SNPs of RGS2 may contribute to the effectiveness of ARB in female EHT patients. These findings would be important to establish individualized medicine for hypertension based on genetic information.