Uromodulin associates with cardiorenal function in patients with hypertension and cardiovascular disease.

Abstract

Common genetic variants in the gene encoding uromodulin (UMOD) have been associated with renal function, blood pressure (BP) and hypertension. We investigated the associations between an important single nucleotide polymorphism (SNP) in UMOD, that is rs12917707-G>T, and estimated glomerular filtration rate (eGFR), BP and cardiac organ damage as determined by echocardiography in patients with arterial hypertension. A cohort of 1218 treated high-risk patients (mean age 58.5 years, 83% men) with documented cardiovascular disease (81% with coronary heart disease) was analysed. The mean values for 24-h SBP and DBP were 124.7 ± 14.7 and 73.9 ± 9.4 mmHg; mean eGFR was 77.5 ± 18.3 ml/min per 1.73 m, mean left ventricular ejection fraction was 59.3 ± 9.9% and mean left ventricular mass index in men and women was 53.9 ± 23.2 and 54.9 ± 23.7 g/m with 50.4% of patients having left ventricular hypertrophy. A significant association between rs12917707 and eGFR was observed with T-allele carriers showing significantly higher eGFR values (+2.6 ml/min per 1.73 m, P = 0.006) than noncarriers. This SNP associated also with left atrial diameter (P = 0.007); homozygous carriers of the T-allele had smaller left atrial diameter (-1.5 mm) than other genotype groups (P = 0.040). No significant associations between rs12917707 and other cardiac or BP phenotypes were observed. These findings extend the previously documented role of UMOD for renal function also to treated high-risk patients with arterial hypertension and reveal a novel association with left atrial remodelling and thus a potential cardiorenal link modulated by UMOD.