title: Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus.
abstract: The organic cation transporter 1, encoded by the SLC22A1 gene, is responsible for the uptake of the anti-hyperglycaemic drug, metformin, in the hepatocyte. We assessed whether a genetic variation in the SLC22A1 gene is associated with the glucose-lowering effect of metformin. Incident metformin users in the Rotterdam Study, whose HbA1c measurements were available, were identified. Associations between 11 tagging single nucleotide polymorphisms in the SLC22A1 gene and change in the HbA1c level were analyzed. A total of 102 incident metformin users were included in this study sample. Except for the rs622342 A>C polymorphism, no significant differences in metformin response were observed. For each minor C allele at rs622342, the reduction in HbA1c levels was 0.28% less (95% CI 0.09-0.47, P=0.005). After Bonferroni correction, the P-value was 0.050. To conclude, genetic variation at rs622342 in the SLC22A1 gene was associated with the glucose-lowering effect of metformin in patients with diabetes mellitus.
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: M L
authors.initials: ML
authors.lastname: Becker
authors.forename: L E
authors.initials: LE
authors.lastname: Visser
authors.forename: R H N
authors.initials: RH
authors.lastname: van Schaik
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: A G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: B H C
authors.initials: BH
authors.lastname: Stricker
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism*; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008297:Male; D008687:Metformin; D050811:Octamer Transcription Factor-1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D008687:Metformin; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human