Association of Serum Uromodulin and Genetic Variants With Blood Pressure Changes, and Hypertension in Chinese Adults: Results From Two Prospective Cohorts

Abstract

Objective: Uromodulin is a novel tissue-specific biomarker for kidney function. We sought to examine the associations of serum uromodulin and genetic variants with salt sensitive and longitudinal blood pressure (BP) changes, or hypertension in humans. Design and method: Subjects (n = 514) from the Baoji Salt-Sensitive Study cohort recruited in 2004 were on the chronic salt intake intervention. We evaluated them for the development of hypertension in 2009 and 2012. In addition, a total of 2210 participants from the Hanzhong Adolescent Hypertension Study cohort were used to examine the relationships between serum uromodulin and the risk of hypertension. Results: We found that SNPs rs12708631 and rs1291770 in the uromodulin gene were significantly associated with longitudinal changes in BPs. SNP rs7198000 was significantly associated with incident hypertension over an 8-year follow-up. Several SNPs was significantly associated with diastolic BP, mean arterial pressure and pulse pressure responses to both low-salt and high-salt diets. Gene-based analyses also supported the overall association of uromodulin gene with longitudinal BP changes and hypertension incidence. In addition, hypertensive subjects have lower levels of serum uromodulin than normotensive subjects. Serum uromodulin showed a linear association with increased BP (34.6, 33.2, 27.8, 27.1 and 26.1 ng/mL for subjects with normotension, high-normal, grade 1, grade 2 and grade 3 hypertension, respectively). Serum uromodulin was significantly associated with the lower risk of hypertension in 2210 Chinese subjects. Conclusions: This study shows that uromodulin gene is associated with salt sensitive and longitudinal BP changes, or hypertension incidence, and serum uromodulin may serve as a biomarker marker for hypertension.