ABSTRACT
Genetic variants in UMOD associate with kidney function and hypertension. These phenotypes are also linked to sex-related differences and impairment in cognitive and physical function in older age. Here we evaluate longitudinal associations between a common UMOD rs4293393-A>G variant and changes in estimated glomerular filtration rate (eGFR), blood pressure (BP), cognitive and physical function parameters in older participants in the BASE-II after long-term follow-up as part of the GendAge study. Overall, 1010 older participants (mean age 75.7 ± 3.7 years, 51.6% women) were analyzed after follow-up (mean 7.4 years) both in cross-sectional analysis and in longitudinal analysis as compared to baseline. In cross-sectional analysis, heterozygous G-allele carriers exhibited significantly higher eGFR values (AA, 71.3 ml/min/1.73 m2, 95% CI, 70.3-72.3 vs. AG, 73.5 ml/min/1.73 m2, 95% CI, 72.1-74.9, P = 0.033). Male heterozygous G-allele carriers had lower odds of eGFR < 60 mL/min/1.73 m2 (OR 0.51, 95% CI, 0.28-0.95, P = 0.032) and in Timed Up and Go-Test ≥ 10 s (OR 0.50, 95% CI, 0.29-0.85, P = 0.011) whereas women were less likely to have hypertension (OR 0.58, CI, 0.37-0.91, P = 0.018). UMOD genotypes were not significantly associated with longitudinal changes in any investigated phenotype. Thus, while the impact of UMOD rs4293393 on kidney function is maintained in aging individuals, this variant has overall no impact on longitudinal changes in BP, kidney, cognitive or functional phenotypes. However, our results suggest a possible sex-specific modifying effect of UMOD on eGFR and physical function in men and hypertension prevalence in women.
Subject(s)
Hypertension , Male , Humans , Female , Blood Pressure/genetics , Cross-Sectional Studies , Hypertension/diagnosis , Hypertension/epidemiology , Hypertension/genetics , Kidney , Glomerular Filtration Rate , Cognition , Uromodulin/geneticsABSTRACT
In genome-wide association studies, genetic variants in the UMOD gene associate with kidney function, blood pressure (BP), and hypertension. Elevated BP is linked to kidney function and impaired cognitive as well as physical performance in later life. We investigated the association between UMOD rs4293393-A > G and kidney function, BP, cognitive and physical function in the Berlin Aging Study II (BASE-II). Data of 1556 older BASE-II participants (mean age 68.2 ± 3.7 years) were analyzed. BP was determined by standardized automated measurements, estimated glomerular filtration rate (eGFR) by CKD Epidemiology Collaboration creatinine equation. Cognitive function was assessed by Mini-Mental State Examination and Digit Symbol Substitution Test, while physical function by Handgrip Strength and Timed Up and Go-Test. Association analyses were performed by covariance and logistic regression models adjusting for sex. G-allele carriers at UMOD rs4293393 exhibited significantly higher eGFR values compared to non-carriers (AA, 76.4 ml/min/1.73 m², CI: 75.7-77.2 vs. AG, 78.4 ml/min/1.73 m², CI: 77.3-79.5 vs. GG, 78.5 ml/min/1.73 m², CI: 75.4-81.7; P = 0.010), and a lower risk of eGFR < 60 mL/min/1.73 m2 (AG, OR: 0.63, CI: 0.41-0.97, P = 0.033). However, UMOD rs4293393 genotypes were not associated with BP, diagnosis of hypertension or cognitive and physical function parameters. Our data corroborate previous findings on the association of UMOD rs4293393-G with better kidney function in older adults. However, no association between UMOD and BP or physical and cognitive parameters in these community-dwelling older adults was detected.
Subject(s)
Hypertension , Renal Insufficiency, Chronic , Humans , Aged , Middle Aged , Blood Pressure/genetics , Genome-Wide Association Study , Hand Strength , Glomerular Filtration Rate/physiology , Hypertension/diagnosis , Hypertension/epidemiology , Hypertension/genetics , Kidney , Cognition , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/genetics , Uromodulin/geneticsABSTRACT
INTRODUCTION: The use of unattended automated office blood pressure (uAutoOBP) versus attended automated (aAutoOBP) and manual auscultatory office blood pressure (AuscOBP) measurements is a topic of current controversy. AIM: To evaluate the differences between OBP measurements methods in the general practice (GP) setting. METHODS: We first compared aAutoOBP and uAutoOBP in 42 consecutive patients with hypertension (group 1). Secondly, we compared AuscOBP to uAutoOBP measurements in 133 consecutive patients with hypertension (group 2). In addition, we analyzed the achieved OBP targets as recommended in the 2018 European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) guidelines in group 2. RESULTS: The mean age of patients in group 1 was 71 years (range 34-89 years, 54.8% females). The aAutoOBP and uAutoOBP systolic (131.7 and 131.6 mmHg) and diastolic (83.4 and 82.4 mmHg) mean values were not significantly different. The patient characteristics in group 2 were similar to group 1. We observed a significant difference between AuscOBP and uAutoOBP measurement for both systolic (149.4 versus 129.5 mm Hg) and diastolic (85.4 versus 81.6 mm Hg, p < 0.0001, respectively). Accordingly, 20.3% and 45.9% of patients reached the overall 2018 ESC/ESH systolic and diastolic OBP targets of < 140/80 mmHg according to AuscOBP and uAutoOBP (p < 0.0001). CONCLUSION: The attended versus unattended status of automated OBP measurements had no impact on OBP values in GP. However, significantly higher OBP values and lower rates of achieved target OBP were observed by using AuscOBP measurements by physicians in comparison to automated OBP recordings.