Journal
DRUG METABOLISM AND PHARMACOKINETICS
Volume 29, Issue 2, Pages 208-210Publisher
JAPANESE SOC STUDY XENOBIOTICS
DOI: 10.2133/dmpk.DMPK-13-NT-070
Keywords
SLC transporter; urate transporter; gouty arthritis; subtype analysis; clinical classification
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Ministry of Health, Labour and Welfare of Japan
- Ministry of Defense of Japan
- Japan Society for the Promotion of Science
- Kawano Masanori Memorial Foundation for Promotion of Pediatrics
- Gout Research Foundation of Japan
- AstraZeneca VRI Research Grant
- Grants-in-Aid for Scientific Research [26461244] Funding Source: KAKEN
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Gout, a common disease, is a consequence of hyperuricemia, and increases the risks of hypertension, cardiovascular diseases, cerebrovascular diseases and renal failure. Gout can be classified into 3 types: the renal underexcretion (RUE) type, renal overload type and combined type. RUE type is a major type of gout; however, its genetic causes are still unclear. Since human organic anion transporter 4 (OAT4/SLC22A11) is expressed in the kidney and mediates urate transport, we investigated the effects of a common variant of OAT4/SLC22A11 on the susceptibility to gout. Five hundred and forty-five Japanese male gout cases and 1,115 male individuals as a control group were genotyped with rs17300741, a single nucleotide polymorphism in the OAT4/SLC22A11 gene. The association analysis of rs17300741 showed no significant association for all gout cases; however, there was a slight but significant association for RUE type gout cases (p = 0.049). These results also suggest that OAT4 contributes to urate transport at the apical membrane of renal proximal tubule cells in humans. Our findings make it clear for the first time that a common variant of OAT4/SLC22A11 is associated with RUE type gout, a major gout subtype.
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