P0157GENETICALLY DETERMINED HYPOALBUMINEMIA AND THE RISK OF HYPERTENSION: GWAS-BASED INSTRUMENTAL VARIABLE ANALYSIS

Abstract

Abstract Background and Aims Hypoalbuminemia is a clinical indicator of vascular endothelial dysfunction. However, the genetic association of hypoalbuminemia with hypertension has not yet been clarified. We investigated whether genetic variation(s) associated with decreased serum albumin level is deeply related with increased risk of hypertension. Method Mild hypoalbuminemia was defined as a serum albumin concentration of less than 4.0 g/dL. We performed GWAS-based instrumental variable analysis using the population-based cohort data collected from KoGES. Eligible as cases were all native Koreans without significant medical illness and a total 4326 participants were divided in into control (n = 3157) and hypoalbuminemic (n = 1168) according to their serum albumin level. Results Our GWAS revealed that 71 susceptibility loci were associated with mild hypoalbuminemia and subsequent two-stage least squares estimation analysis showed that both genetic variations at rs2894536 in LOC107986598 gene and rs10972486 in the ATP8B5P gene were related with systolic blood pressure. In subsequent Cox-proportional hazards model, we found that not only low serum albumin (HR = 0.654, 95% CI = 0.521-0.820), but also polymorphisms of rs2894536 (HR = 1.176, 95% CI = 1.015-1.361) and rs10972486 (HR = 1.152, 95% CI = 1.009-1.316) were significant predictor of hypertension. Our two-stage residual inclusion analysis indicated that candidate genetic variation attenuated the association between serum albumin and hypertension, showing hazard ratios of hypoalbuminemia on development of hypertension were 0.762 (0.659-0.882) for rs2894536 and 0.759 (0.656-0.878) for rs10972486. Conclusion These findings support a causal relationship between hypoalbuminemia-associated genetic variation, hypoalbuminemia and development of hypertension.