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#52
GENETIC POLYMORPHISM OF NON-SYNONYMOUS AMINO ACID CHANGE OF THE IMPDH-1 GENE IN RENAL PATIENTS.
Mohammad R. Bazrafshani, Dr , Kay V. Poulton, Dr , Faieza J. Qasim, Dr and Philip A. Dyer, Dr . Manchester Lancashire, United Kingdom, Manchester Royal Infirmary, M13 9WL, The Transplantation Laboratory and Manchester Lancashire, United Kingdom, Manchester Royal Infirmary, M13 9WL, Renal Unit .

Background: The enzyme inosine monophosphate dehydrogenase-1 (IMPDH-1) is a target for the immunosuppressive agent mycophenolate mofetil (MMF) because it catalyses a key step in de novo purine nucleotide biosynthesis. This is important for the proliferation of lymphocytes (proliferating B and T lymphocytes are singularly dependent on the de novo pathway). The IMPDH-1 gene is highly polymorphic (30 known polymorphisms) and it may be of interest in predicting individual responses to MMF therapy.
Aim: we investigated population frequencies of IMPDH-1 gene polymorphisms of five non-synonymous amino acid change in renal transplant recipients; to evaluate possible implications for future transplant therapies.
Methods: A total of five polymorphisms were selected for analysis (Asp29Gly, Asn109Lys, Phe273Leu, His274Asp and Ala497Pro). Genotyping assays performed by using PCR-SSP in 96 recipients of renal allograft and 96 kidney donors as controls.
Results: No differences in allele and genotype frequencies were observed for five polymorphisms between the two groups. The heterozygous allele frequencies are shown in the table below:

GenotypeControls (%)Renal Cases (%)
Asp29Gly10.212.8
Asn109Lys19.622.6
Phe273Leu37.529.2
His274Asp19.221.2
Ala497Pro22.023.8


Conclusion: Alleles of five markers studied are present in a UK population with heterozygosity ranging between 10.2-37.5%. It would be interesting to analyse frequencies of these alleles based in ethnic groups who show different responses to MMF therapy. Several other polymorphisms exist in this gene that influence IMPDH-1 activity and we are currently investigating any possible association between those and susceptibility to adverse reactions to MMF therapy.