Risk factors and myocardial infarction in patients with obstructive sleep apnea: impact of beta2-adrenergic receptor polymorphisms.
BACKGROUND
The increased sympathetic nervous activity in patients with obstructive sleep apnea (OSA) is largely responsible for the high prevalence of arterial hypertension, and it is suggested to adversely affect triglyceride and high-density lipoprotein (HDL) cholesterol levels in these patients. The functionally relevant polymorphisms of the beta2-adrenergic receptor (Arg-47Cys/Arg16Gly and Gln27Glu) have been shown to exert modifying effects on these risk factors in previous studies, but results are inconsistent.


METHODS
We investigated a group of 429 patients (55 +/- 10.7 years; 361 men, 68 women) with moderate to severe obstructive sleep apnea (apnea/hypopnea index (AHI) 29.1 +/- 23.1/h) and, on average, a high cardiovascular risk profile (body mass index 31.1 +/- 5.6, with hypertension in 60.1%, dyslipidemia in 49.2%, and diabetes in 17.2% of patients). We typed the beta2-adrenergic receptor polymorphisms and investigated the five most frequent haplotypes for their modifying effects on OSA-induced changes in blood pressure, heart rate, and lipid levels. The prevalence of cardiovascular risk factors and coronary heart disease (n = 55, 12.8%) and survived myocardial infarction (n = 27, 6.3%) were compared between the genotypes and haplotypes.


RESULTS
Multivariate linear/logistic regressions revealed a significant and independent (from BMI, age, sex, presence of diabetes, use of antidiabetic, lipid-lowering, and antihypertensive medication) influence of AHI on daytime systolic and diastolic blood pressure, heart rate, prevalence of hypertension, and triglyceride and HDL levels. The beta2-adrenergic receptor genotypes and haplotypes showed no modifying effects on these relationships or on the prevalence of dyslipidemia, diabetes, and coronary heart disease, yet, for all three polymorphisms, heterozygous carriers had a significantly lower relative risk for myocardial infarction (Arg-47Cys: n = 195, odds ratio (OR) = 0.32, P = 0.012; Arg16Gly: n = 197, OR = 0.39, P = 0.031; Gln27Glu: OR = 0.37, P = 0.023). Carriers of the most frequent haplotype (n = 113) (haplotype 1; heterozygous for all three polymorphisms) showed a five-fold lower prevalence of survived myocardial infarction (OR = 0.21, P = 0.023).


CONCLUSIONS
Our study showed no significant modifying effect of the functionally relevant beta2-adrenergic receptor polymorphisms on OSA-induced blood pressure, heart rate, or lipid changes. Nevertheless, heterozygosity of these polymorphisms is associated with a lower prevalence of survived myocardial infarction in this group with, on average, a high cardiovascular risk profile.
Bartels
Nina K
NK
Human Genetics, Ruhr-University Bochum, Germany. the_sirius@web.de
Börgel
Jan
J
Wieczorek
Stefan
S
Büchner
Nikolaus
N
Hanefeld
Christoph
C
Bulut
Daniel
D
Mügge
Andreas
A
Rump
Lars C
LC
Sanner
Bernd M
BM
Epplen
Jörg T
JT
D000368:Aged; D001794:Blood Pressure; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*
D018343:Receptors, Adrenergic, beta-2