Association of JAG1 gene polymorphism with systemic blood pressure in patients with obstructive sleep apnea: A prospective cohort study

Abstract

Aim To assess the effects of single nucleotide polymorphisms (SNPs) on blood pressure control in patients with obstructive sleep apnea (OSA). Methods This prospective observational cohort study, conducted between 2004 and 2014, examined the associations of SNPs of JAG1, GUCY1A3-GUCY1B3, SH2B3, and NPR3-C5orf23 genes with systolic and diastolic blood pressure (SBP, DBP) in 1179 adults evaluated for OSA with overnight polysomnography. Genotyping was performed by unlabeled probe melting analysis. Results The patients were predominantly male (69.6%, mean age 52 ±11 years, apnea-hypopnea index 34 ±31 episodes/h). Only JAG1 genotype was associated with SBP and DBP: Compared with AA homozygotes, G allele carriers (pooled GG and AG genotype) had significantly higher morning SBP (132 ±19 vs 129 ±18 mm Hg; P = 0.009) and morning and evening DBP (85 ±11 vs 83 ±10 mm Hg, P = 0.004; 86 ±10 vs 84 ±10 mm Hg, P = 0.012, respectively); the differences remained significant after the correction for multiple SNPs testing. In multivariate analyses, oxygen desaturation index and JAG1 genotype independently predicted morning SBP (P = 0.001, P = 0.003, respectively) and DBP (P < 0.001, P = 0.005, respectively), and evening SBP (P = 0.019, P = 0.048, respectively) and DBP (P = 0.018, P = 0.018, respectively). Conclusion This is the first replication study of the SNPs recently linked to arterial hypertension in general population by genome-wide association studies. Our findings suggest that JAG1 genotype is related to blood pressure control in OSA: G allele was associated with higher morning and evening SBP and DBP.