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ß₂-Adrenergic Receptor Genotype and Pulmonary Function in Patients With Heart Failure^*

^* From the Divisions of Cardiovascular Diseases (Drs. Snyder and Johnson) and Nephrology and Hypertension (Dr. Turner), Department of Internal Medicine, Mayo Clinic, Rochester, MN.

Correspondence to: Bruce D. Johnson, PhD, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, 200 First St, SW, Rochester, MN 55905; e-mail: johnson.bruce{at}mayo.edu

Abstract

Objective: Chronic heart failure (CHF) is associated with neurohumoral activation and decrements in pulmonary function (PF). The ß₂-adrenergic receptor (ADRB2) modulates airway smooth muscle tone and influences lung fluid clearance. Common polymorphisms of the ADRB2 are associated with differences in ADRB2 function and therefore could differentially influence PF in patients with CHF.

Methods: We studied baseline PF according to genetic variations of the ADRB2 at amino acid 16 (ie, arginine [Arg] or glycine [Gly]) in 126 CHF patients (mean [± SEM] age, 56 ± 1 years; left ventricular ejection fraction [LVEF], 29 ± 1%; body mass index [BMI], 28 ± 0.4 kg/m²) and in 100 healthy control subjects (mean age, 50 ± 2 years; LVEF, 63 ± 0.7%; BMI, 25 ± 0.3 kg/m²).

Results: Venous epinephrine levels did not differ between CHF patients and control subjects or across genotype groups; however, norepinephrine levels were higher in CHF patients and was greater in ArgArg patients compared to GlyGly patients (p < 0.05). PF did not differ according to genotype in control subjects; however, CHF patients who were homozygous for Arg had reduced PF relative to heterozygotes or those subjects who were homozygous for Gly (vital capacity: ArgArg group, 82 ± 3% predicted; ArgGly group, 92 ± 2% predicted; GlyGly group, 93 ± 2% predicted; FVC: ArgArg group, 77 ± 3% predicted; ArgGly group, 89 ± 2% predicted; GlyGly group, 90 ± 2% predicted; FEV₁: ArgArg group, 75 ± 4% predicted; ArgGly group, 86 ± 3% predicted; GlyGly group, 87 ± 2% predicted; diffusing capacity of the lung for carbon monoxide: ArgArg group, 76 ± 4% predicted; ArgGly group, 83 ± 2% predicted; GlyGly group, 85 ± 2% predicted; p < 0.05). In addition, there was a modest correlation between mitral valve inflow deceleration time and PF in CHF patients (r = 0.42; p < 0.01), but not in control subjects.

Conclusions: These data suggest that genetic variation of the ADRB2 is associated with differences in PF in CHF patients but not in healthy subjects, which may be related to an increased susceptibility of the homozygous Arg subjects to agonist-mediated desensitization of ADRB2s in the lungs, or related to an influence of this polymorphism on cardiac diastolic properties.

Key Words: airway • congestive heart failure • echocardiography • receptors