Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The evolutionary loss of hepatic urate oxidase (uricase) has resulted in humans with elevated serum uric acid (urate). Uricase loss may have been beneficial to early primate survival. However, an elevated serum urate has predisposed man to hyperuricemia, a metabolic disturbance leading to gout, hypertension, and various cardiovascular diseases. Human serum urate levels are largely determined by urate reabsorption and secretion in the kidney. Renal urate reabsorption is controlled via two proximal tubular urate transporters: apical URAT1 (SLC22A12) and basolateral URATv1/GLUT9 (SLC2A9). In contrast, the molecular mechanism(s) for renal urate secretion remain unknown. In this report, we demonstrate that an orphan transporter hNPT4 (human sodium phosphate transporter 4; SLC17A3) was a multispecific organic anion efflux transporter expressed in the kidneys and liver. hNPT4 was localized at the apical side of renal tubules and functioned as a voltage-driven urate transporter. Furthermore, loop diuretics, such as furosemide and bumetanide, substantially interacted with hNPT4. Thus, this protein is likely to act as a common secretion route for both drugs and may play an important role in diuretics-induced hyperuricemia. The in vivo role of hNPT4 was suggested by two hyperuricemia patients with missense mutations in SLC17A3. These mutated versions of hNPT4 exhibited reduced urate efflux when they were expressed in Xenopus oocytes. Our findings will complete a model of urate secretion in the renal tubular cell, where intracellular urate taken up via OAT1 and/or OAT3 from the blood exits from the cell into the lumen via hNPT4.
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PMID:Human sodium phosphate transporter 4 (hNPT4/SLC17A3) as a common renal secretory pathway for drugs and urate. 2081 Jun 51

In this article there were analyzed gender data about features of hyperuricaemia and gout: women are much older at the onset of gout arthritis (one of main reasons, probably, makes menopause by itself), have more associated comorbid deseases as hypertension and kidney failure and drinks less alcoholic beverages. It was noticed, that typical localisation of the lesion on the first toe is less often in women, and women are more inclined to use diuretics among medical drugs. Abovementioned clinical features are of some importance for the broad activity of general practitioners - family doctors. Gender features of polyarthicular gout are not uniformed. Scientific researches confirmed possibility of the genetic basis of the uric acid metabolism, which influences some fenotypical features of the organism. Several genes are known for their influence on serum uric acid: PDZK1, GCKR, SLC2A9, ABCG2, LRRC16A, SLC17A3, SLC16A9 and SLC22A12. However, conclusions of the research works confirm the necessity of scientific clarification of the importance of different factors of gender differences.
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PMID:[Importance of the hyperuricaemia, gout and gender nosological features in the activity of general practitioner - family doctor]. 2353 71