Uromodulin levels associate with a common UMOD variant and risk for incident CKD.
Common variants in the region of the UMOD gene, which encodes uromodulin (Tamm-Horsfall protein), associate with chronic kidney disease (CKD) and estimated GFR (eGFR). Whether uromodulin levels associate with UMOD variants or with the risk for developing CKD is unknown. We conducted an age- and gender-matched case-control study (n = 200) of incident CKD (eGFR <60 ml/min per 1.73 m(2)) within the Framingham Heart Study (FHS). Baseline urinary uromodulin concentrations were related to case-control status 9.9 yr later and to genotype at rs4293393. As a replication set, we tested the genotype association with uromodulin concentration in the Atherosclerosis Risk in Communities (ARIC) Study (n = 42). Geometric means of uromodulin concentrations were 51% higher in case than in control subjects (P = 0.016). The adjusted odds ratio of CKD per 1-SD higher concentration of uromodulin was 1.72 (95% confidence interval 1.07 to 2.77; P = 0.03) after accounting for CKD risk factors and baseline eGFR. We observed lower urinary uromodulin concentrations per each copy of the C allele at rs4293393 in both cohorts. In summary, elevated uromodulin concentrations precede the onset of CKD and associate with a common polymorphism in the UMOD region.
Köttgen
Anna
A
73 Mount Wayte Avenue, Suite #2, Framingham, MA 01702, USA.
Hwang
Shih-Jen
SJ
Larson
Martin G
MG
Van Eyk
Jennifer E
JE
Fu
Qin
Q
Benjamin
Emelia J
EJ
Dehghan
Abbas
A
Glazer
Nicole L
NL
Kao
W H Linda
WH
Harris
Tamara B
TB
Gudnason
Vilmundur
V
Shlipak
Michael G
MG
Yang
Qiong
Q
Coresh
Josef
J
Levy
Daniel
D
Fox
Caroline S
CS
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics* / Q000503:physiopathology / Q000652:urine*; D052177:Kidney Diseases, Cystic / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000235:genetics; D009088:Mucoproteins / Q000235:genetics* / Q000652:urine*; D018995:Myosin Heavy Chains / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D058949:Uromodulin
C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D009088:Mucoproteins; C548612:UMOD protein, human; D058949:Uromodulin; D018995:Myosin Heavy Chains