BETA1 (ARG389GLY, SER49GLY)- AND BETA2 (ARG16GLY)-ADRENOCEPTOR POLYMORPHISMS ARE RELATED TO LEFT VENTRICULAR HYPERTROPHY USING ECG IN MIDDLE-AGED, NORMOTENSIVE SUBJECTS: PP.22.358

Abstract

Objective: Left ventricular hypertrophy (LVH) accompanying elevated sympathetic nervous activity (SNA) is more common in hypertensive and obese people. Elevated SNA is an important mechanism in cardiovascular complications and cardiac morbidity and mortality. β2-adrenoceptor (ADRB2) polymorphisms are closely linked to hypertension and obesity, and β1-adrenoceptor (ADRB1) play roles directly with the heart. We evaluated the relationships between ADRB1 polymorphisms, ADRB2 polymorphisms and LVH. Methods: In 215 nonobese, normotensive Japanese men, ADRB1 polymorphisms (Arg389Gly, Ser49Gly), ADRB2 polymorphisms (Arg16Gly, Gln27Glu), BMI, BP, heart rates (HR), total body fat-mass, waist-to-hip ratio (W/H), plasma norepinephrine (NE), insulin, leptin and ECG were measured. LVH was determined by the Sokolow-Lyon voltage criteria. Results: Twenty-four subjects (11.2%) showed LVH on ECG. Subjects with LVH had higher NE, BP levels and HR compared to those without LVH (all P < 0.05), but BMI, fat-mass, W/H, insulin and leptin were similar. Subjects with LVH had higher frequencies of Gly389 or Gly49 alleles of ADRB1 polymorphisms (χ2 = 49.94, P = 0.002; χ2 = 11.43, P = 0.001, respectively), and Gly16 or Glu27 alleles of ADRB2 polymorphisms (χ2 = 9.59, P = 0.002; χ2 = 3.12, P = 0.059, respectively). Distributions of Gly389 and Gly49 alleles of ADRB1 polymorphisms and Gly16 and Glu27 alleles of ADRB2 were 39.5%, 27.9%, 74.4% and 11.2%, respectively. Subjects with Gly389 or Gly49 had higher frequencies of LVH, higher NE and HR (all P < 0.05), whereas BMI, fat-mass, W/H, BP, insulin and leptin were similar. Subjects with Gly16 had higher frequencies of LVH and greater BMI, fat-mass, systolic BP, NE and insulin compared to those without Gly16 allele (all P < .05). In multiple regression analysis, plasma NE was a significant determinant for systolic BP and LVH in all subjects. Conclusions: Subjects carrying Gly389 and Gly49 alleles of ADRB1 polymorphisms and Gly16 allele of ADRB2 polymorphisms had higher frequency of LVH accompanying high plasma NE. ADRB1 polymorphisms might relate to LVH directly through elevated SNA, but ADRB2 polymorphisms might relate to LVH through obesity and hypertension associated with elevated SNA and insulin resistance.