title: Pharmacogenomic association between a variant in SLC47A1 gene and therapeutic response to metformin in type 2 diabetes.
abstract: Pharmacogenetic studies revealed that variants in genes related to the pharmacokinetics of metformin were associated with glucose-lowering effect of metformin. The aim of this study was to investigate possible associations of the variants in genes encoding organic cationic transporters-solute carrier family 22, members A1, A2 (SLC22A1, SLC22A2) and solute carrier family 47, member A1 (SLC47A1) with response to metformin in type 2 diabetes. One hundred forty-eight drug-naive patients with type 2 diabetes were included in the study. Genotyping for SLC22A1 rs622342, SLC22A2 rs316019 and SLC47A1 rs2289669 variants was performed using real-time PCR with subsequent melting-curve analysis. SLC47A1 rs2289669 genotype was significantly associated with the reduction in haemoglobin A1c (HbA1c) after 6 months. Twenty percentage of patients with diabetes that are homozygous for A-allele of SLC47A1 had twofold reduction in HbA1c in comparison with the patients carrying G-allele (GG + GA: 0.55 ± 0.09% vs. AA: 1.10 ± 0.18%, p = 0.018). In conclusion, the results of this study might have in future practical implication in personalised treatment of patients with type 2 diabetes.
authors.affiliation: Department of Internal Medicine 4, Faculty of Medicine, Šafárik University, Košice, Slovakia. Ivan.Tkac@upjs.sk
authors.forename: I
authors.initials: I
authors.lastname: Tkáč
authors.forename: L
authors.initials: L
authors.lastname: Klimčáková
authors.forename: M
authors.initials: M
authors.lastname: Javorský
authors.forename: M
authors.initials: M
authors.lastname: Fabianová
authors.forename: Z
authors.initials: Z
authors.lastname: Schroner
authors.forename: H
authors.initials: H
authors.lastname: Hermanová
authors.forename: E
authors.initials: E
authors.lastname: Babjaková
authors.forename: R
authors.initials: R
authors.lastname: Tkáčová
mesh_terms: D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008875:Middle Aged; D027701:Organic Cation Transport Proteins; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D027701:Organic Cation Transport Proteins; C521869:SLC47A1 protein, human; D008687:Metformin