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A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes

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A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes : a replication and meta-analysis of five cohorts. / 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 (Lead / Corresponding author); Pearson, Ewan (Lead / Corresponding author).

In: Diabetologia, Vol. 55, No. 7, 2012, p. 1971-1977.

Research output: Contribution to journalArticle

Harvard

van Leeuwen, N, Nijpels, G, Becker, ML, Deshmukh, H, Zhou, K, Stricker, BHC, Uitterlinden, AG, Hofman, A, van 't Riet, E, Palmer, CNA, Guigas, B, Slagboom, PE, Durrington, P, Calle, RA, Neil, A, Hitman, G, Livingstone, SJ, Colhoun, H, Holman, RR, McCarthy, MI, Dekker, JM, 't Hart, LM & Pearson, E 2012, 'A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes: a replication and meta-analysis of five cohorts' Diabetologia, vol 55, no. 7, pp. 1971-1977.

APA

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. (2012). A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes: a replication and meta-analysis of five cohorts. Diabetologia, 55(7), 1971-1977doi: 10.1007/s00125-012-2537-x

Vancouver

van Leeuwen N, Nijpels G, Becker ML, Deshmukh H, Zhou K, Stricker BHC et al. A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes: a replication and meta-analysis of five cohorts. Diabetologia. 2012;55(7):1971-1977.

Author

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 (Lead / Corresponding author); Pearson, Ewan (Lead / Corresponding author) / A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes : a replication and meta-analysis of five cohorts.

In: Diabetologia, Vol. 55, No. 7, 2012, p. 1971-1977.

Research output: Contribution to journalArticle

Bibtex - Download

@article{8b6be18bc15e4551ae979d397738715a,
title = "A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes",
author = "{van Leeuwen}, N and G Nijpels and Becker, {M L} and H Deshmukh and K Zhou and Stricker, {B H C} and Uitterlinden, {A G} and A Hofman and {van 't Riet}, E and Palmer, {C N A} and B Guigas and Slagboom, {P E} and P Durrington and Calle, {R A} and A Neil and G Hitman and Livingstone, {S J} and H Colhoun and Holman, {R R} and McCarthy, {M I} and Dekker, {J M} and {'t Hart}, {L M} and Ewan Pearson",
year = "2012",
volume = "55",
number = "7",
pages = "1971--1977",
journal = "Diabetologia",
issn = "0012-186X",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes

T2 - a replication and meta-analysis of five cohorts

A1 - van Leeuwen,N

A1 - Nijpels,G

A1 - Becker,M L

A1 - Deshmukh,H

A1 - Zhou,K

A1 - Stricker,B H C

A1 - Uitterlinden,A G

A1 - Hofman,A

A1 - van 't Riet,E

A1 - Palmer,C N A

A1 - Guigas,B

A1 - Slagboom,P E

A1 - Durrington,P

A1 - Calle,R A

A1 - Neil,A

A1 - Hitman,G

A1 - Livingstone,S J

A1 - Colhoun,H

A1 - Holman,R R

A1 - McCarthy,M I

A1 - Dekker,J M

A1 - 't Hart,L M

A1 - Pearson,Ewan

AU - van Leeuwen,N

AU - Nijpels,G

AU - Becker,M L

AU - Deshmukh,H

AU - Zhou,K

AU - Stricker,B H C

AU - Uitterlinden,A G

AU - Hofman,A

AU - van 't Riet,E

AU - Palmer,C N A

AU - Guigas,B

AU - Slagboom,P E

AU - Durrington,P

AU - Calle,R A

AU - Neil,A

AU - Hitman,G

AU - Livingstone,S J

AU - Colhoun,H

AU - Holman,R R

AU - McCarthy,M I

AU - Dekker,J M

AU - 't Hart,L M

AU - Pearson,Ewan

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1007/s00125-012-2537-x

DO - 10.1007/s00125-012-2537-x

M1 - Article

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 7

VL - 55

SP - 1971

EP - 1977

ER -

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