Abstract 2588: AT1-R, ADDI, Per3 and Cry1 Gene Polymorphism may Influence the Antihypertensive Effect of β Blockers
Objective: Genetic background is thought to influence the effectiveness of β blockers. The aim of the present study is to clarify the relating susceptible single nucleotide polymorphisms (SNPs) to the effectiveness of β blockers in patients with essential hypertension (EHT).
Methods: We evaluated averaged blood pressure (BP) of 109 EHT patients, measured on three consecutive outpatient clinic visits, before and after taking β blockers. We genotyped 28 genes, 84 SNPs related to adrenergic receptors (2 ADRB1, 4 ADRB2, 1 ADRA1A, 1 ADRA1B, 1 ADRA2A, 1ADRA2B, 2 DRD3, 1 DBH ), renin-angiotensin aldosterone system (2 AGTN, 8 ACE, 2 ACE2, 2AT1-R, 1 CYP11B2, 3 MLR), salt sensitivity (1 ADDI), signal transduction (1 GNB3, 1 PI3K, 6 RGS2, 1 tyrosine hydroxylase genes) and circadian rhythm related genes (1 BMAL1, 2 CK1e, 3 Clock, 4 CRY1, 5 DBP, 8 MOP4, 4 Per1, 4 Per2, 12 Per3) by TaqMan PCR method.
Results: Systolic (S) and Diastolic (D) BP were significantly lowered after β blocker treatment. There were significant differences of ΔBP (BP post-BP pre) between the genotypes of AT1-R (all subjects; AT1-R -153A>G; ΔSBP; AA (n=86) -11.9±16.1 vs. GA (n=21) -3.3±14.1 mmHg, p<0.05, ΔDBP; AA -6.7±8.0 vs. GA -2.3±9.8 mmHg, p<0.05, female subjects; ΔSBP; AA (n=32) -12.50±15.7 vs. GA (n=9) 4.0±17.3 mmHg, p<0.01). There were also significant differences of ΔSBP and ΔDBP in female subjects between the genotypes of ADDI G460W polymorphism. (ΔSBP; 460W/W (n=15) -1.3±14.3, 460G/G+W/G (n=26) -13.3±17.5 mmHg, p<0.05, ΔDBP; 460W/W -1.0±6.0, 460G/G+W/G -6.7±7.3 mmHg, p<0.05 ) As for the circadian rhythm related genes, there were significant differences of ΔSBP between the wild and variant types of Per3 7319C>T (CC (n=23) -14.2±17.5, TT+CT (n=17) -2.0±15.2 mmHg, p<0.05) and Per3 TTA] 20974 (Ins (n=31) -5.6±13.9, Del (n=10) -19.2±22.9 mmHg, p<0.05) polymorphisms in female subjects. In male subjects, there was a significant difference of ΔDBP between the genotypes of Cry1 1698C>T (CC (n=54) -5.5±9.1, TT+CT (n=11) -11.6±8.0 mmHg, p<0.05.)
Conclusions: The five SNPs of AT1-R, ADDI, Per3 and Cry1 may contribute to the effectiveness of β blockers in patients with EHT. These findings would be important to establish individualized medicine for hypertension based on genetic information.