Interpopulation Variation Frequency of Human Inosine 5′-Monophosphate Dehydrogenase Type II (IMPDH2) Genetic Polymorphisms

Inosine monophosphate dehydrogenase type II (IMPDH2) is the target for immunosuppression by mycophenolic acid and has been linked to resistance of tumor cells to chemotherapy. Determining the frequency of IMPDH2 genetic polymorphisms can inform the design of clinical studies investigating the impact of IMPDH2 genetic variability on both cancer therapy and immunosuppression. Frequencies of three IMPDH2 polymorphisms (rs4974081, rs5848860, and rs11557540) in >400 DNA samples from four different racial/ethnic groups (Caucasian, African American, Hispanic, and Asian populations) were characterized by the pyrosequencing genotyping method. For rs5848860 1591 CTT/-(500 G/EG) and rs11557540 1345 A/G (418 D/G), we did not observe any variant alleles in all DNA samples from these populations, which suggests that these variants could simply be sequencing errors rather than real polymorphisms. The observed frequency of the 5'-upstream single-nucleotide polymorphism (SNP) rs4974081 A/G was similar to that previously reported in the NCBI databank (dbSNP). An in silico functional analysis using FASTSNP predicts that this promoter SNP rs4974081 (-3624 A/G) could be a potential transcription factor binding site. This finding suggests that rs4974081 could be a good candidate SNP for association studies with immunosuppressive and chemotherapeutic therapy outcomes.