Pharmacogenetics of the mycophenolic acid targets inosine monophosphate dehydrogenases IMPDH1 and IMPDH2: gene sequence variation and functional genomics.

ABSTRACT:

Background and purpose

Inosine monophosphate dehydrogenases, encoded by IMPDH1 and IMPDH2, are targets for the important immunosuppressive drug, mycophenolic acid (MPA). Variation in MPA response may result, in part, from genetic variation in IMPDH1 and IMPDH2.

Experimental approach

We resequenced IMPDH1 and IMPDH2 using DNA from 288 individuals from three ethnic groups and performed functional genomic studies of the sequence variants observed.

Key results

We identified 73 single nucleotide polymorphisms (SNPs) in IMPDH1, 59 novel, and 25 SNPs, 24 novel, in IMPDH2. One novel IMPDH1 allozyme (Leu275) had 10.2% of the wild-type activity as a result of accelerated protein degradation. Decreased activity of the previously reported IMPDH2 Phe263 allozyme was primarily due

SUBMITTER: Wu TY 

PROVIDER: S-EPMC3010569 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature