title: Uromodulin levels associate with a common UMOD variant and risk for incident CKD.
abstract: 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.
authors: 73 Mount Wayte Avenue, Suite #2, Framingham, MA 01702, USA.
authors: Anna
authors: A
authors: Köttgen
authors: Shih-Jen
authors: SJ
authors: Hwang
authors: Martin G
authors: MG
authors: Larson
authors: Jennifer E
authors: JE
authors: Van Eyk
authors: Qin
authors: Q
authors: Fu
authors: Emelia J
authors: EJ
authors: Benjamin
authors: Abbas
authors: A
authors: Dehghan
authors: Nicole L
authors: NL
authors: Glazer
authors: W H Linda
authors: WH
authors: Kao
authors: Tamara B
authors: TB
authors: Harris
authors: Vilmundur
authors: V
authors: Gudnason
authors: Michael G
authors: MG
authors: Shlipak
authors: Qiong
authors: Q
authors: Yang
authors: Josef
authors: J
authors: Coresh
authors: Daniel
authors: D
authors: Levy
authors: Caroline S
authors: CS
authors: Fox
mesh_terms: 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
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D009088:Mucoproteins; C548612:UMOD protein, human; D058949:Uromodulin; D018995:Myosin Heavy Chains