title: Inter-ethnic variability of three functional polymorphisms affecting the IMPDH2 gene.
abstract: Human type II inosine monophosphate dehydrogenase (IMPDH2) is a key enzyme in the purine nucleotide biosynthetic pathway and constitutes a pivotal biological target for immunosuppressant and antiviral drugs. Several Single Nucleotide Polymorphisms (SNP) affecting the IMPDH2 gene sequence have been reported with potential functional relevance and could impact drugs response. We aimed to determine the frequency of three of these polymorphisms, namely g.3375C>T (Leu(263)Phe), c.-95T>G and IVS7+10T>C, in Caucasians, Tunisians, Peruvians and Black Africans (Gabonese and Senegalese). The g.3375C>T and c.-95T>G polymorphisms are rare with a Minor Allele Frequency ≤1.0% in our populations, whereas the third variant, IVS7+10T>C, is more frequent and displays large interethnic variations, with an allelic frequency ranging from 14.6% in the French Caucasian population studied to less than 2% in Black African and Peruvian populations. This ethnic-related data might contribute to a better understanding of the variability in clinical outcome and/or dose adjustments of drugs that are IMPDH inhibitors such as mycophenolic acid.
authors.affiliation: Equipe D'accueil 4483, Faculté de Médecine de Lille, Pôle Recherche, 1 place de Verdun, 59045 Lille Cedex, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Garat
authors.forename: Christian Lacks Lino
authors.initials: CL
authors.lastname: Cardenas
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lionet
authors.forename: Aurore
authors.initials: A
authors.lastname: Devos
authors.forename: François
authors.initials: F
authors.lastname: Glowacki
authors.forename: Abderraouf
authors.initials: A
authors.lastname: Kenani
authors.forename: Florence
authors.initials: F
authors.lastname: Migot-Nabias
authors.forename: Delphine
authors.initials: D
authors.lastname: Allorge
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lo-Guidice
authors.forename: Franck
authors.initials: F
authors.lastname: Broly
authors.forename: Christelle
authors.initials: C
authors.lastname: Cauffiez
mesh_terms: D005006:Ethnicity / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics*; D059645:Mutation Rate; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D007168:IMP Dehydrogenase; C501687:IMPDH2 protein, human