Association of ACE and PAI-1 gene polymorphisms with clinical outcomes of obstructive sleep apnea

Abstract: Obstructive sleep apnoea (OSA) is a sleeping disorder leading to complications such as daytime-sleepiness, migraines and snoring and is often associated with coronary artery disease (CAD). Studies have suggested the contribution of genetic factors in aetiology of OSA. Angiotensin converting enzyme (ACE) is involved in the regulation of blood pressure and PAI-1 (plasminogen activator-inhibitor-1 encoded by SERPINE1) in fibrinolysis and breakdown of blood clots; both of these two proteins are implicated in OSA. In the present work potential correlation between OSA, and two single nucleotide polymorphisms in ACE (rs4646994, deletion/insertion of ALU sequence) and SERPINE1 (rs1799764, 4G/5G) genes were examined in a Swedish CAD cohort. Chi-square test, Kruskal-Wallis test, Mann–Whitney U test and multinomial logistics regression were used to analyse the genotyping data. A significant correlation between the heterozygote genotype at ACE rs4646994 and incidence of OSA was identified. The distribution of SERPINE1 rs1799764 genotypes was not in equilibrium in the cohort with the most prevalent homozygous 4G/4G genotype, suggesting a correlation between this genotype and development of CAD. No significant association between rs1799764 genotypes and occurrence of OSA or PAI-1 serum levels was found. However, a significant association between the rs1799764 4G/4G genotype and uncontrolled blood pressure was identified. High PAI-1 serum levels were additionally found to be associated with obesity and angiotensin II receptor-blockers. In summary, our analysis suggested ACE rs4646994 heterozygote genotype is strongly correlated with OSA and its severity, and there is a strong correlation between SERPINE1 rs1799764 homozygote 4G/4G genotype and uncontrollable blood pressure.