913 common genetic background for hypertension, metabolic syndrome traits and resting heart rate in microalbuminuric subjects

Objectives: 1. To identify the impact of metabolic syndrome (MetS) components on risk of microalbuminuria (MAU). 2. To examine the association between validated hypertension and type-2 diabetes (T2D) susceptibility genes and MetS traits with resting heart rate (HR) in microalbuminuric individuals. Methods: 1. In the Czech Post-Monica study, we examined a representative population sample (n=3612) for MAU and MetS. 2. We conducted genome-wide association case-control study using Affymetrix SNP Array 6.0. Cases (n= 63) with MAU and MetS were age- and sex-matched with controls (n=63) without MAU and MetS, while cases (n=31) from the upper extreme of the ACR distribution curve were matched to their controls (n=31) irrespective of MetS. Only individuals without hypertension, T2D and cardiovascular disease (CVD) were eligible as controls. Results: 1. MetS was independently associated with MAU (p<0.0001). Hypertension was independent predictor of MAU (p=0.022) after adjusting for MetS components and confounders. 2. We report an association between 3SNPs in hypertension CACNB2 gene and MetSy (p=0.0005), hypertension (p=0.0006) and TG (p=0.00008). We found an association between SNPs in T2D gene GLIS3 and MetS, CVD and hypertension; TCF7L2 and MetS; GCKR and hypertension; CAMK1D, IGF2BP2 and resting HR. In multivariate regression, rs1017568 in GLIS3 (p=0.007) and rs4918790 in TCF7L2 genes (p=0.0002) were independent predictors of MAU. When summing up risk alleles of SNPs in T2D genes, the OR for MAU per genetic risk score unit was 1.085 ([CI 1.04-1.13], p=0.0003). Conclusion: Association between MAU and the MetS is based on common genetic background conferring higher cardiovascular risk.