Variation in the glucose transporter gene SLC2A2 is associated with glycaemic response to metformin
Metformin is the first-line antidiabetic drug with over 100 million users worldwide, yet its mechanism of action remains unclear1. Here the Metformin Genetics (MetGen) Consortium reports a three-stage genome-wide association study (GWAS), consisting of 13,123 participants of different ancestries. Th...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
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Nature Publishing Group
2016
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| _version_ | 1826273276123414528 |
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| author | Kaixin, Z Yee, S Seiser, E van Leeuwen, N Tavendale, R Bennett, A Groves, C Coleman, R van der Heijden, A Beulens, J de Keyser, C Zaharenko, L Rotroff, D Out, M Jablonski, K Chen, L Javorský, M Židzik, J Levin, A William, L Dujic, T Semiz, S Kubo, M Chien, H Maeda, S Witte, J Wu, L Tkáč, I Kooy, A van Schaik, R Stehouwer, C Logie, L MetGen Investigators DPP Investigators ACCORD Investigators Sutherland, C Klovins, J Pirags, V Hofman, A Stricker, B Motsinger-Reif, A Wagner, M Innocenti, F 't Hart, L Holman, R McCarthy, M Hedderson, M Palmer, C Florez, J Giacomini, K Pearson, E |
| author_facet | Kaixin, Z Yee, S Seiser, E van Leeuwen, N Tavendale, R Bennett, A Groves, C Coleman, R van der Heijden, A Beulens, J de Keyser, C Zaharenko, L Rotroff, D Out, M Jablonski, K Chen, L Javorský, M Židzik, J Levin, A William, L Dujic, T Semiz, S Kubo, M Chien, H Maeda, S Witte, J Wu, L Tkáč, I Kooy, A van Schaik, R Stehouwer, C Logie, L MetGen Investigators DPP Investigators ACCORD Investigators Sutherland, C Klovins, J Pirags, V Hofman, A Stricker, B Motsinger-Reif, A Wagner, M Innocenti, F 't Hart, L Holman, R McCarthy, M Hedderson, M Palmer, C Florez, J Giacomini, K Pearson, E |
| author_sort | Kaixin, Z |
| collection | OXFORD |
| description | Metformin is the first-line antidiabetic drug with over 100 million users worldwide, yet its mechanism of action remains unclear1. Here the Metformin Genetics (MetGen) Consortium reports a three-stage genome-wide association study (GWAS), consisting of 13,123 participants of different ancestries. The C allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (P = 6.6 × 10−14) greater metformin-induced reduction in hemoglobin A1c (HbA1c) in 10,577 participants of European ancestry. rs8192675 was the top cis expression quantitative trait locus (cis-eQTL) for SLC2A2 in 1,226 human liver samples, suggesting a key role for hepatic GLUT2 in regulation of metformin action. Among obese individuals, C-allele homozygotes at rs8192675 had a 0.33% (3.6 mmol/mol) greater absolute HbA1c reduction than T-allele homozygotes. This was about half the effect seen with the addition of a DPP-4 inhibitor, and equated to a dose difference of 550 mg of metformin, suggesting rs8192675 as a potential biomarker for stratified medicine. |
| first_indexed | 2024-03-06T22:25:44Z |
| format | Journal article |
| id | oxford-uuid:569d2974-7b69-473a-b4e9-3295ffdf4d9b |
| institution | University of Oxford |
| last_indexed | 2024-03-06T22:25:44Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:569d2974-7b69-473a-b4e9-3295ffdf4d9b2022-03-26T16:51:24ZVariation in the glucose transporter gene SLC2A2 is associated with glycaemic response to metforminJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:569d2974-7b69-473a-b4e9-3295ffdf4d9bSymplectic Elements at OxfordNature Publishing Group2016Kaixin, ZYee, SSeiser, Evan Leeuwen, NTavendale, RBennett, AGroves, CColeman, Rvan der Heijden, ABeulens, Jde Keyser, CZaharenko, LRotroff, DOut, MJablonski, KChen, LJavorský, MŽidzik, JLevin, AWilliam, LDujic, TSemiz, SKubo, MChien, HMaeda, SWitte, JWu, LTkáč, IKooy, Avan Schaik, RStehouwer, CLogie, LMetGen InvestigatorsDPP InvestigatorsACCORD InvestigatorsSutherland, CKlovins, JPirags, VHofman, AStricker, BMotsinger-Reif, AWagner, MInnocenti, F't Hart, LHolman, RMcCarthy, MHedderson, MPalmer, CFlorez, JGiacomini, KPearson, EMetformin is the first-line antidiabetic drug with over 100 million users worldwide, yet its mechanism of action remains unclear1. Here the Metformin Genetics (MetGen) Consortium reports a three-stage genome-wide association study (GWAS), consisting of 13,123 participants of different ancestries. The C allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (P = 6.6 × 10−14) greater metformin-induced reduction in hemoglobin A1c (HbA1c) in 10,577 participants of European ancestry. rs8192675 was the top cis expression quantitative trait locus (cis-eQTL) for SLC2A2 in 1,226 human liver samples, suggesting a key role for hepatic GLUT2 in regulation of metformin action. Among obese individuals, C-allele homozygotes at rs8192675 had a 0.33% (3.6 mmol/mol) greater absolute HbA1c reduction than T-allele homozygotes. This was about half the effect seen with the addition of a DPP-4 inhibitor, and equated to a dose difference of 550 mg of metformin, suggesting rs8192675 as a potential biomarker for stratified medicine. |
| spellingShingle | Kaixin, Z Yee, S Seiser, E van Leeuwen, N Tavendale, R Bennett, A Groves, C Coleman, R van der Heijden, A Beulens, J de Keyser, C Zaharenko, L Rotroff, D Out, M Jablonski, K Chen, L Javorský, M Židzik, J Levin, A William, L Dujic, T Semiz, S Kubo, M Chien, H Maeda, S Witte, J Wu, L Tkáč, I Kooy, A van Schaik, R Stehouwer, C Logie, L MetGen Investigators DPP Investigators ACCORD Investigators Sutherland, C Klovins, J Pirags, V Hofman, A Stricker, B Motsinger-Reif, A Wagner, M Innocenti, F 't Hart, L Holman, R McCarthy, M Hedderson, M Palmer, C Florez, J Giacomini, K Pearson, E Variation in the glucose transporter gene SLC2A2 is associated with glycaemic response to metformin |
| title | Variation in the glucose transporter gene SLC2A2 is associated with glycaemic response to metformin |
| title_full | Variation in the glucose transporter gene SLC2A2 is associated with glycaemic response to metformin |
| title_fullStr | Variation in the glucose transporter gene SLC2A2 is associated with glycaemic response to metformin |
| title_full_unstemmed | Variation in the glucose transporter gene SLC2A2 is associated with glycaemic response to metformin |
| title_short | Variation in the glucose transporter gene SLC2A2 is associated with glycaemic response to metformin |
| title_sort | variation in the glucose transporter gene slc2a2 is associated with glycaemic response to metformin |
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