Effect of a common UMOD variant on kidney function, blood pressure, cognitive and physical function in a community-based cohort of older adults

Abstract

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.