Abstract 5161:β 1 (Arg389Gly, Ser49Gly)- and β2 (Arg16Gly) -adrenoceptor Polymorphisms are Related to Left Ventricular Hypertrophy in Middle-aged, Nonobese, Normotensive Men, but Through Different Mechanisms
Objective: β2-adrenoceptor (ADRB2) polymorphisms are closely linked to hypertension and obesity, and both of them are major cardiac risk. Left ventricular hypertrophy (LVH) is more common in people who have hypertension or obesity. We examined the relationships between ADRB1 and ADRB2 polymorphisms and LVH in nonobese, normotensive subjects.
Methods: In 447 middle-aged, normotensive, nonobese men, ADRB1 (Arg389Gly, Ser49Gly) and ADRB2 (Arg16Gly, Gln27Glu) polymorphisms, BMI, BP, heart rates (HR), total body fat-mass, waist-to-hip ratio (W/H), plasma norepinephrine (NE) and ECG were measured after overnight fasting in the supine position. LVH was determined by ECG.
Results: Thirty-nine subjects (8.7%) showed LVH on ECG. Subjects with LVH had higher plasma NE and HR compared to those without LVH (both P<.05). Distributions of Gly389 and Gly49 alleles of ADRB1 polymorphisms were 23.5% (Arg/Arg:Arg/Gly:Gly/Gly=270:144:33) and 14.1% (Ser/Ser:Ser/ Gly:Gly/Gly=327:114:6). Thirty-seven subjects with LVH (94.9%) carried Gly389 and Gly49 alleles, especially homozygous for Gly389 or Gly49. Subjects with Gly389 or Gly49 alleles had higher frequencies of LVH (20.9% vs. 0.7%, 30.8% vs. 0.6%). Subjects carrying Gly389 or Gly49 alleles had higher plasma NE and HR (both P<.05), whereas BMI, fat mass, W/H and BP were similar. The Gly16 and Glu27 alleles of ADRB2 polymorphisms were noted in 42.8% (Arg/Arg :Arg/Gly:Gly/Gly=69:245:133) and 36.6% of the subjects (Gln/Gln:Gln/Glu:Glu/ Glu=176:215:56). Twenty-nine subjects with LVH (74.4%) carried Gly16 allele, especially Gly16 homozygous. Subjects with Gly16 allele had higher frequencies of LVH (P<.05), and they had greater BMI, fat mass, W/H, BP, HR and NE compared to those without Gly16 allele (all P<.05).
Conclusions: Subjects carrying Gly389 and Gly49 alleles of ADRB1 polymorphisms and Gly16 allele of ADRB2 polymorphism had higher frequency of LVH accompanying high plasma NE. ADRB1 and ADRB2 polymorphisms play important roles in LVH even in nonobese, normotensive subjects. ADRB1 polymorphisms might relate to LVH through heightened sympathetic nerve activity, but ADRB2 polymorphisms might relate to LVH through obesity, hypertension and heightened sympathetic nerve activity.