| Theme |
Therapeutic strategy for ulcerative colitis ; from standard to up-to-date |
| Title |
The multidrug-resistance protein 4 polymorphism accounts for thiopurine sensitivity in Japanese patients with inflammatory bowel disease |
| Author |
Akira Andoh |
Division of Mucosal Immunology, Graduate School, Shiga University of Medical Science |
| Author |
Hiromitsu Ban |
Department of Medicine, Shiga University of Medical Science |
| Author |
Rie Osaki |
Department of Medicine, Shiga University of Medical Science |
| Author |
Hirotsugu Imaeda |
Department of Medicine, Shiga University of Medical Science |
| [ Summary ] |
Multidrug resistance protein 4 (MRP4) functions as an efflux pump of nucleoside monophosphate analogs, such as 6-mercaptopurine (6-MP) and 6-thioguanine nucleotide (6-TGN). A single-nucleotide polymorphism in human MRP4 (rs3765534) dramatically reduces MRP4 function, and results in the intracellular accumulation of 6-TGN. Of the 279 samples analyzed (44 healthy volunteers and 235 IBD patients), 68 samples showed a heterozygote of MRP4 G2269A, and 7 carried a homozygote. The allelic frequency of MRP4 G2269A was 14.7 %. In 130 IBD patients treated with azathioprine (AZA)/6-MP, the WBC count was significantly lower in patients with the MRP4 variant alone (n=26) than in patients with a wild allelotype (n=74)(P=0.014) or in patients with the ITPase variant alone (n=22)(P=0.0095). The 6-TGN levels were significantly higher in patients with the MRP4 variant alone than patients with the wild allelotype (P=0.049). MRP4 G2269A might be a new factor accounting for thiopurine sensitivity in Japanese patients with IBD. |