Genetic polymorphisms in endothelin-receptor-subtype-a-gene as susceptibility factor for obstructive sleep apnea...

Traits of obstructive sleep apnea syndrome (OSAS) such as impaired ventilatory control, craniofacial abnormalities, and concomitant cardiovascular diseases are associated with modified endothelin-1 gene (EDN-1) or endothelin-receptor-subtype-a (EDNRA) gene. The endothelin system regulates the cardiovascular homeostasis. EDN-1 interacts mainly with EDNRA for signal transduction. In our study we investigate associations of EDNRA-polymorphisms (four frequent polymorphisms with an allele frequency >5%) and OSAS severity.

Three hundred ninety-three patients older than 18years, of Caucasian origin and with OSAS (AHI>5/h and daytime sleepiness) were investigated by cardiorespiratory polysomnography. In addition 58 control subjects with healthy sleep were recruited from nearly 300 volunteers. We analysed the EDNRA-polymorphisms E335E, H323H, G-231A and G+70C by polymerase-chain-reaction, restriction-fragment-length-polymorphism and real-time-PCR.

Carrier of the mutant G-231A allele had a significantly lower AHI (p=0.03, OR 0.53, 95% CI 0.3-0.94) when comparing patients and controls. When comparing OSAS severity groups without controls we could not detect significant correlations for the four investigated EDNRA-polymorphisms. Our data confirm that BMI (p<0.001) and male gender (p=0.02) are significantly associated with AHI. The allele frequencies were similar.

The genetic investigation of OSA remains important. Our control group was relatively small and we investigated 4 reasonable candidates out of more than 100 EDNRA-polymorphisms. The detected protective effect of the mutant G-231A allele needs further confirmation. Gene based research in OSAS should use genome wide scan and should still consider the endothelin system.