1. ¹Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands
2. ²Department of Hospital Pharmacy, Erasmus MC, Rotterdam, The Netherlands
3. ³Department of Clinical Chemistry, Erasmus MC, Rotterdam, The Netherlands
4. ⁴STAR Medical Diagnostic Center, Rotterdam, The Netherlands
5. ⁵Member of The Netherlands Consortium on Healthy Aging, Leiden/Rotterdam, The Netherlands
6. ⁶Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
7. ⁷Drug Safety Unit, Inspectorate for Health Care, The Hague, The Netherlands

Correspondence: Professor BHC Stricker, Department of Epidemiology, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands. E-mail: b.stricker@erasmusmc.nl

Received 13 January 2009; Revised 4 March 2009; Accepted 16 March 2009; Published online 21 April 2009.

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.