title: Endothelin-1 gene variant Lys198Asn and plasma endothelin level in obstructive sleep apnea.
abstract: Obstructive sleep apnea (OSA) is a recognized risk factor for cardiovascular disorders. Thus, an association between endothelin-1 (EDN1) and OSA can be assumed. We investigated a cohort of 364 consecutive patients (age 57 +/- 10 years) with mild to severe OSA for the EDN1 variant Lys198Asn (G/T) and endothelin plasma levels and compared them with 57 controls. The Lys198Asn genotype was significantly associated with the apnea/hypopnea index (AHI) with a median of 30/h of sleep for GG, 27/h for GT and 59/h for TT genotype (p < 0.05). Further stratification of patients into 2 groups by body mass index (BMI) revealed a strong association between AHI and Lys198Asn polymorphism in 191 obese patients (p = 0.005), whereas in 173 nonobese patients, we observed no association. A substantial effect by BMI on OSA severity was seen with multiple linear regression (p < 0.001). However, this effect was modified by the Lys198Asn polymorphism and by gender: the AHI increase per unit of BMI was more pronounced in males than in females, and about 1.3 times greater in homozygous carriers of the mutant allele than in other carrier groups. EDN1 plasma levels of untreated OSA patients and of patients treated with nasal continuous positive airway pressure were not elevated compared with controls. Our results indicate that the Lys198Asn polymorphism is associated with the severity of OSA in obese subjects. The EDN1 plasma level cannot be used as a marker for OSA or its severity.
authors.affiliation: Institute of Clinical Pharmacology, Charité - Universitatsmedizin Berlin, Berlin, Germany.
authors.forename: Konstanze
authors.initials: K
authors.lastname: Diefenbach
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kretschmer
authors.forename: Steffen
authors.initials: S
authors.lastname: Bauer
authors.forename: Uwe
authors.initials: U
authors.lastname: Malzahn
authors.forename: Thomas
authors.initials: T
authors.lastname: Penzel
authors.forename: Ivar
authors.initials: I
authors.lastname: Roots
authors.forename: Ingo
authors.initials: I
authors.lastname: Fietze
mesh_terms: D000368:Aged; D019332:Endothelin-1 / Q000097:blood* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics; D017354:Point Mutation; D012307:Risk Factors; D012720:Severity of Illness Index; D020181:Sleep Apnea, Obstructive / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D019332:Endothelin-1