Haptoglobin polymorphism is a risk factor for cardiovascular disease in patients with obstructive sleep apnea syndrome.
OBJECTIVE
Obstructive sleep apnea syndrome is associated with a marked increase in the risk for cardiovascular disease. Increased oxidative stress and leukocyte adhesiveness have been implicated as fundamental pathophysiologic mechanisms underlying the increased susceptibility in these patients. Haptoglobin is an antioxidant and immunomodulatory protein encoded by 2 alleles with profoundly different biophysical and biochemical properties. We therefore sought to determine if the haptoglobin phenotype was a determinant of cardiovascular disease in patients with obstructive sleep apnea syndrome.


METHODS
Haptoglobin phenotype was determined by gel electrophoresis in 465 patients with and 757 individuals without obstructive sleep apnea syndrome.


METHODS
Eight-bed Technion Sleep Medicine Center in Haifa, serving the northern part of Israel.


METHODS
Patients referred for sleep recordings because of suspected breathing disorders in sleep and healthy industry workers.


RESULTS
Patients with obstructive sleep apnea syndrome and cardiovascular disease had a significantly different distribution of the 3 haptoglobin phenotypes as compared to patients with obstructive sleep apnea syndrome but without cardiovascular disease. No difference in the haptoglobin phenotype frequency was found between controls with and without cardiovascular disease. Log linear analysis revealed a significant interaction effect of haptoglobin phenotype and the presence of sleep apnea on the presence of cardiovascular disease. Logistic regression analysis revealed that the risk of cardiovascular disease in sleep apnea patients younger than 55 years with haptoglobin 2-2 was 2.32-fold higher than in their counterparts with haptoglobin 2-1.


CONCLUSIONS
These results suggest that haptoglobin phenotype is an important risk factor in determining susceptibility to cardiovascular disease in obstructive sleep apnea syndrome, which may be mediated by the decreased antioxidant and antiinflammatory actions of the haptoglobin 2 allelic protein product.
Lavie
Lena
L
Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Lotan
Rachel
R
Hochberg
Irit
I
Herer
Paula
P
Lavie
Peretz
P
Levy
Andrew P
AP
D000483:Alleles; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index; D020181:Sleep Apnea, Obstructive / Q000175:diagnosis / Q000453:epidemiology*
D006242:Haptoglobins