Association of Â-adrenergic receptor polymorphisms and nocturnal cardiopulmonary coupling in the skara sleep cohort

Abstract

Electrocardiogram (ECG) based cardiopulmonary coupling (CPC) analysis has been used for assessment of fragmented sleep and sleep disordered breathing. We investigated the relationships between â1- and â2- adrenergic receptor (AR) gene polymorphisms and CPC in a gender-balanced community-dwelling cohort of hypertensive patients and normotensive controls (Skara Sleep Cohort). 280 subjects (137 males, 126 hypertensive patients, age 61.3 ± 6.5 years, BMI 28.5 ± 4.7 kg/m 2 , AHI 24.6 ± 22.1 events/hour) underwent home polysomnography recording. The ECG signal was used to calculate the coupling between heart-rate variability oscillations and ECG-derived respiration. The percentage time spent with high-frequency coupling (HFC, 0.1–0.4 Hz), low-frequency coupling (LFC, 0.01–0.1 Hz) and very low-frequency coupling (VLFC, 0.0039–0.01 Hz) during the sleep period was quantified in subjects with various AR genotypes (â1-[Ser49Gly, Gly389Arg] and â2-[Gly16Arg, Gln27Glu]). The â2-AR Arg16 homozygous group had a higher HFC and lower LFC than the Gly16 group independent of gender, total apnea/hypopnea count and sleep efficiency ( p = 0.026 and 0.011, respectively). The â1-AR Arg389 and Gly389 homozygous groups differed in terms of time spent with HFC and VLFC ( p = 0.067 and 0.003, respectively). There was a significant interaction between â2-AR Arg16Gly and â1-AR Arg389Gly polymorphisms such that â2-AR Arg16 homozygotes had further increased HFC and reduced LFC when â1-AR Gly389 allele was present. The â1-AR Ser49Gly and â2-AR Gln27Glu genotypes did not associate with CPC indices. The â2-AR Arg16Gly polymorphism influences CPC during sleep. Difference in the â-AR genotype may explain variations in cardiac autonomic modulation during sleep. The study was supported by the Swedish Heart and Lung Foundation, the Swedish Society of Medicine and the Göteborg Medical Society.