Abstract
Background: Uromodulin, also named Tamm Horsfall protein, has been associated with renal function and regulation of sodium homeostasis. We aimed to examine the associations of serum uromodulin levels and its genetic variants with longitudinal blood pressure (BP) changes and hypertension incidence/risk.Methods: A total of 514 participants from the original Baoji Salt-Sensitive Study cohort were genotyped to examine the associations of genetic variations in uromodulin gene with the longitudinal BP changes and the incidence of hypertension over 8 years of follow-up. In addition, 2,210 subjects from the cohort of Hanzhong Adolescent Hypertension Study were used to investigate the relationships between serum uromodulin levels and the risk of hypertension.Results: SNPs rs12917707 and rs12708631 in the uromodulin gene were significantly associated with the longitudinal BP changes over 8 years of follow-up. SNP rs12708631 was significantly associated with the incidence of hypertension over 8 years. In addition, gene-based analyses supported the associations of uromodulin gene with the longitudinal BP changes and hypertension incidence in Baoji Salt-Sensitive Study cohort. Furthermore, serum uromodulin levels in the hypertensive subjects were lower than in the normotensive subjects (25.5 ± 1.1 vs. 34.7 ± 0.7 ng/mL). Serum uromodulin levels decreased gradually as BP levels increased (34.6, 33.2, 27.8, and 25.0 ng/mL for subjects with normotension, high-normal, grade 1 hypertension, and grade 2 hypertension, respectively). Serum uromodulin was significantly associated with the lower risk of hypertension [0.978 (0.972–0.984)] in Hanzhong Adolescent Hypertension Study cohort.Conclusion: This study shows that uromodulin is associated with blood pressure progression and development of hypertension.
Highlights
Hypertension, due to its high prevalence and its associated risk of cardiovascular disease and all-cause mortality, is considered as a major worldwide public health challenge [1, 2]
The entire study consisted of two parts: [1] a longitudinal cohort study to explore the associations of UMOD gene with longitudinal blood pressure (BP) changes and hypertension incidence; and [2] a cross-sectional cohort study to examine the relationships between serum uromodulin levels and the risk of hypertension
The age of the participants was 48.6 years, body mass index (BMI) was 22.2 kg/m2, and the mean Systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) were 115.2, 71.3, and 86.0 mmHg, respectively. 51 (9.9%) subjects were diagnosed with hypertension at baseline
Summary
Hypertension, due to its high prevalence and its associated risk of cardiovascular disease and all-cause mortality, is considered as a major worldwide public health challenge [1, 2]. Uromodulin, known as Tamm-Horsfall protein, is a 95 kDa glycoprotein. Prior studies showed that genetic variants in the UMOD gene were associated with BP phenotypes and hypertension [16,17,18]. No study has yet explored the associations of common variants in the UMOD gene with the longitudinal BP changes or the incidence of hypertension. Data are scarce about the relationship between serum uromodulin levels and the risk of hypertension. Uromodulin, named Tamm Horsfall protein, has been associated with renal function and regulation of sodium homeostasis. We aimed to examine the associations of serum uromodulin levels and its genetic variants with longitudinal blood pressure (BP) changes and hypertension incidence/risk
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