Beta‐2 adrenergic receptor haplotype and echocardiographic indices in heart failure patients

Abstract

We recently reported altered cardiovascular structure and function in heart failure (HF) patients based on the Arg16/Gly and Gln27/Glu beta‐2 adrenergic receptor (ADRB2) polymorphisms. The purpose of this study was to extend the echocardiographic analysis based on haplotype combination of ADRB2 at nucleotides −654, 46 79, 252, 491, 523, in a larger database of HF patients (n=126, age 56±1yr, LV ejection fraction, LVEF 29±1%, BMI 28±0.4kg/m2, mean±SEM) and healthy controls (n=100, age 50±2yr, LVEF 63±0.7%, BMI 25±0.3kg/m2). The most common haplotypes in both HF and control were 2, 8, and 12 (2=AACGCC, 8=GGCACA, and 12=GGGGCC, for nucleotides −654, 46, 79, 252, 491, and 523). Cardiac function did not differ according to haplotype pairs in the control subjects. In HF, the widest discrepancies were between haplotype pair 2/2 (which includes the Arg16+Gln27 homozygotes) and haplotype pair 12/12 (which includes the Gly16+Glu27 homozygotes), respectively: 2/2 displayed lower cardiac index (2.3±0.1 v 2.7±0.1 l/min/m2), greater left atrial diameter (53±2 v 47±2 mm), shorter LV decel time (185±11 v 224±14 msec), and greater right ventricular pressure (44±2 v 33±2 mmHg) p<0.05 for all). These data suggest that in HF, haplotype variation of the ADRB2 is associated with differences in cardiac function, and SNP positions 16 and 27 remain major loci of interest.Support: K23RR‐17520, HL‐71478.