Details

Autor(en) / Beteiligte

• van Leeuwen, N.
• Nijpels, G.
• Becker, M. L.
• Deshmukh, H.
• Zhou, K.
• Stricker, B. H. C.
• Uitterlinden, A. G.
• Hofman, A.
• van ’t Riet, E.
• Palmer, C. N. A.
• Guigas, B.
• Slagboom, P. E.
• Durrington, P.
• Calle, R. A.
• Neil, A.
• Hitman, G.
• Livingstone, S. J.
• Colhoun, H.
• Holman, R. R.
• McCarthy, M. I.
• Dekker, J. M.
• ’t Hart, L. M.
• Pearson, E. R.

Titel

A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes: a replication and meta-analysis of five cohorts

Ist Teil von

• Diabetologia, 2012-07, Vol.55 (7), p.1971-1977

Ort / Verlag

Berlin/Heidelberg: Springer-Verlag

Erscheinungsjahr

2012

Quelle

springer (창간호~2014)

Beschreibungen/Notizen

• Aims/hypothesis In this study we aimed to replicate the previously reported association between the glycaemic response to metformin and the SNP rs11212617 at a locus that includes the ataxia telangiectasia mutated ( ATM ) gene in multiple additional populations. Methods Incident users of metformin selected from the Diabetes Care System West-Friesland (DCS, n  = 929) and the Rotterdam Study ( n  = 182) from the Netherlands, and the CARDS Trial ( n  = 254) from the UK were genotyped for rs11212617 and tested for an association with both HbA 1c reduction and treatment success, defined as the ability to reach the treatment target of an HbA 1c ≤7 % (53 mmol/mol). Finally, a meta-analysis including data from literature was performed. Results In the DCS cohort, we observed an association between rs11212617 genotype and treatment success on metformin (OR 1.27, 95% CI 1.03, 1.58, p  = 0.028); in the smaller Rotterdam Study cohort, a numerically similar but non-significant trend was observed (OR 1.45, 95% CI 0.87, 2.39, p  = 0.15); while in the CARDS cohort there was no significant association. In meta-analyses of these three cohorts separately or combined with the previously published cohorts, rs11212617 genotype is associated with metformin treatment success (OR 1.24, 95% CI 1.04, 1.49, p  = 0.016 and OR 1.25, 95% CI 1.33, 1.38, p  = 7.8 × 10 −6 , respectively). Conclusions/interpretation A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetic patients from the Netherlands and the UK. This is the first robustly replicated common susceptibility locus found to be associated with metformin treatment response.