[Molecular basis of primary renal hyperuricemia : role of the human urate transporter hURAT1].
In highly industrialized countries hyperuricemia is one of the most common metabolic disorders. High uric acid blood levels may lead to the manifestation of gout owing to the precipitation of urate crystals in connective tissue, the skeletal system and kidneys. A primary reduction of renal uric acid excretion can be detected in more than 90% of all cases of hyperuricemia. Despite the identification of several uric acid transporting proteins their pathogenetic role for the induction of primary reduced renal uric acid excretion has not yet been verified. As a result of a case-control study on individuals with normal and reduced renal uric acid excretion, an association of polymorphisms in the human urate transporter 1 gene (hURAT1) with primary reduced urate excretion has been demonstrated for the first time. The hURAT1 gene is an organic anion transporter (SLC22A12), which is preferentially expressed in the apical membrane of proximal renal tubule cells. Functioning as an antiporter, hURAT1 mediates the uptake of urate from the lumen into proximal tubule cells in exchange for organic and inorganic anions. Loss-of-function mutations in the hURAT1 gene are a cause of hereditary renal hypouricemia. The precisely regulated hURAT1 is a candidate gene for hyperuricemia and an important target for the development and optimization of new diagnostic approaches and pharmacological interventions of primary reduced renal uric acid excretion.
Unger
S
S
Bereich Pathologische Biochemie, Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Deutschland.
Tausche
A-K
AK
Kopprasch
S
S
Bornstein
S R
SR
Aringer
M
M
Grässler
J
J
D015210:Arthritis, Gouty / Q000175:diagnosis / Q000235:genetics* / Q000652:urine; D005819:Genetic Markers / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D033461:Hyperuricemia / Q000175:diagnosis / Q000235:genetics* / Q000652:urine; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D027361:Organic Anion Transporters / Q000235:genetics*; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D014527:Uric Acid / Q000652:urine*
D005819:Genetic Markers; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; D014527:Uric Acid