A Two-Stage Study Identifies Two Novel Polymorphisms in PRKAG2 Affecting Metformin Response in Chinese Type 2 Diabetes Patients

References

• Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract. 2019;157:107843. doi:10.1016/j.diabres.2019.107843
   PubMed Web of Science ®Google Scholar
• Wang L, Gao P, Zhang M, et al. Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013. JAMA. 2017;317:2515–2523. doi:10.1001/jama.2017.7596
   PubMed Web of Science ®Google Scholar
• Xu Y. Prevalence and control of diabetes in Chinese adults. JAMA. 2013;310:948–959. doi:10.1001/jama.2013.168118
   PubMed Web of Science ®Google Scholar
• Upadhyay J. Pharmacotherapy of type 2 diabetes: an update. Metabolism. 2018;78:13–42.
   PubMed Web of Science ®Google Scholar
• American Diabetes Association.9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2020. Diabetes Care. 2020;43:S98–S110. doi:10.2337/dc20-S009
   Web of Science ®Google Scholar
• Esposito K, Chiodini P, Bellastella G, Maiorino MI, Giugliano D. Proportion of patients at HbA1c target <7% with eight classes of antidiabetic drugs in type 2 diabetes: systematic review of 218 randomized controlled trials with 78 945 patients. Diabetes Obes Metab. 2012;14:228–233.
   PubMed Web of Science ®Google Scholar
• McCreight LJ, Bailey CJ, Pearson ER. Metformin and the gastrointestinal tract. Diabetologia. 2016;59:426–435. doi:10.1007/s00125-015-3844-9
   PubMed Web of Science ®Google Scholar
• Dujic T, Zhou K, Tavendale R, Palmer CN, Pearson ER. Effect of Serotonin Transporter 5-HTTLPR polymorphism on gastrointestinal intolerance to metformin: a GoDARTS Study. Diabetes Care. 2016;39:1896–1901. doi:10.2337/dc16-0706
   PubMed Web of Science ®Google Scholar
• Shu Y, Brown C, Castro RA, et al. Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics. Clin Pharmacol Ther. 2008;83:273–280. doi:10.1038/sj.clpt.6100275
   PubMed Web of Science ®Google Scholar
• Dujic T, Zhou K, Yee SW, et al. Variants in pharmacokinetic transporters and glycemic response to metformin: a metgen meta-analysis. Clin Pharmacol Ther. 2017;101:763–772. doi:10.1002/cpt.567
   PubMed Web of Science ®Google Scholar
• Zaharenko L, Kalnina I, Geldnere K, et al. Single nucleotide polymorphisms in the intergenic region between metformin transporter OCT2 and OCT3 coding genes are associated with short-term response to metformin monotherapy in type 2 diabetes mellitus patients. Eur J Endocrinol. 2016;175:531–540. doi:10.1530/EJE-16-0347
   PubMed Web of Science ®Google Scholar
• Xiao D, Guo Y, Li X, et al. The Impacts of SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms on metformin therapeutic efficacy in Chinese type 2 diabetes patients. Int J Endocrinol. 2016;2016:4350712. doi:10.1155/2016/4350712
   PubMed Web of Science ®Google Scholar
• Choi JH, Yee SW, Ramirez AH, et al. A common 5ʹ-UTR variant in MATE2-K is associated with poor response to metformin. Clin Pharmacol Ther. 2011;90:674–684. doi:10.1038/clpt.2011.165
   PubMed Web of Science ®Google Scholar
• Tkac I, Klimčáková L, Javorský M, et al. Pharmacogenomic association between a variant in SLC47A1 gene and therapeutic response to metformin in type 2 diabetes. Diabetes Obes Metab. 2013;15:189–191. doi:10.1111/j.1463-1326.2012.01691.x
   PubMed Web of Science ®Google Scholar
• Chen S, Zhou J, Xi M, et al. Pharmacogenetic variation and metformin response. Curr Drug Metab. 2013;14:1070–1082. doi:10.2174/1389200214666131211153933
   Web of Science ®Google Scholar
• Han TK, Proctor WR, Costales CL, et al. Four cation-selective transporters contribute to apical uptake and accumulation of metformin in Caco-2 cell monolayers. J Pharmacol Exp Ther. 2015;352:519–528. doi:10.1124/jpet.114.220350
   PubMed Web of Science ®Google Scholar
• Liang X, Chien H-C, Yee SW, et al. Metformin is a substrate and inhibitor of the human thiamine transporter, THTR-2 (SLC19A3. Mol Pharm. 2015;12:4301–4310. doi:10.1021/acs.molpharmaceut.5b00501
   PubMed Web of Science ®Google Scholar
• Zhou K. Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nat Genet. 2011;43:117–120.
   PubMed Web of Science ®Google Scholar
• Zhou K, Yee SW, Seiser EL, et al. Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin. Nat Genet. 2016;48:1055–1059. doi:10.1038/ng.3632
   PubMed Web of Science ®Google Scholar
• Rotroff DM, Yee SW, Zhou K, et al. Genetic Variants in CPA6 and PRPF31 are associated with variation in response to metformin in individuals with type 2 diabetes. Diabetes. 2018;67:1428–1440. doi:10.2337/db17-1164
   PubMed Web of Science ®Google Scholar
• Florez JC, Jablonski KA, Taylor A, et al. The C allele of ATM rs11212617 does not associate with metformin response in the Diabetes Prevention Program. Diabetes Care. 2012;35:1864–1867. doi:10.2337/dc11-2301
   PubMed Web of Science ®Google Scholar
• van Leeuwen N, Nijpels G, Becker ML, 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;55:1971–1977. doi:10.1007/s00125-012-2537-x
   PubMed Web of Science ®Google Scholar
• Out M, Becker ML, van Schaik RH, et al. A gene variant near ATM affects the response to metformin and metformin plasma levels: a post hoc analysis of an RCT. Pharmacogenomics. 2018;19:715–726. doi:10.2217/pgs-2018-0010
   Web of Science ®Google Scholar
• Ji L, Tong X, Wang H, et al. Efficacy and safety of traditional Chinese medicine for diabetes: a double-blind, randomised, controlled trial. PLoS One. 2013;8:e56703. doi:10.1371/journal.pone.0056703
   Web of Science ®Google Scholar
• Sesti G, Marini MA, Cardellini M, et al. The Arg972 variant in insulin receptor substrate-1 is associated with an increased risk of secondary failure to sulfonylurea in patients with type 2 diabetes. Diabetes Care. 2004;27:1394–1398. doi:10.2337/diacare.27.6.1394
   PubMed Web of Science ®Google Scholar
• Ren Q, Xiao D, Han X, et al. Genetic and clinical predictive factors of sulfonylurea failure in patients with type 2 diabetes. Diabetes Technol Ther. 2016;18:586–593. doi:10.1089/dia.2015.0427
   PubMed Web of Science ®Google Scholar
• Fagerholm V, Scheinin M, Haaparanta M. alpha2A-adrenoceptor antagonism increases insulin secretion and synergistically augments the insulinotropic effect of glibenclamide in mice. Br J Pharmacol. 2008;154:1287–1296. doi:10.1038/bjp.2008.186
   Web of Science ®Google Scholar
• Zhou K, Donnelly L, Burch L, et al. Loss-of-function CYP2C9 variants improve therapeutic response to sulfonylureas in type 2 diabetes: a Go-DARTS study. Clin Pharmacol Ther. 2010;87:52–56. doi:10.1038/clpt.2009.176
   PubMed Web of Science ®Google Scholar
• Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017;60:1577–1585. doi:10.1007/s00125-017-4342-z
   PubMed Web of Science ®Google Scholar
• Grahame Hardie D. AMP-activated protein kinase: a key regulator of energy balance with many roles in human disease. J Intern Med. 2014;276:543–559. doi:10.1111/joim.12268
   PubMed Web of Science ®Google Scholar
• Xiao B, Sanders MJ, Carmena D, et al. Structural basis of AMPK regulation by small molecule activators. Nat Commun. 2013;4:3017. doi:10.1038/ncomms4017
   PubMed Web of Science ®Google Scholar
• Willows R, Navaratnam N, Lima A, Read J, Carling D. Effect of different gamma-subunit isoforms on the regulation of AMPK. Biochem J. 2017;474:1741–1754. doi:10.1042/BCJ20170046
   Web of Science ®Google Scholar
• Ross FA, Jensen TE, Hardie DG. Differential regulation by AMP and ADP of AMPK complexes containing different gamma subunit isoforms. Biochem J. 2016;473:189–199. doi:10.1042/BJ20150910
   PubMed Web of Science ®Google Scholar
• Yavari A, Stocker C, Ghaffari S, et al. Chronic Activation of gamma2 AMPK induces obesity and reduces beta cell function. Cell Metab. 2016;23:821–836. doi:10.1016/j.cmet.2016.04.003
   Web of Science ®Google Scholar
• Jablonski KA, McAteer JB, de Bakker PIW, et al. Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program. Diabetes. 2010;59:2672–2681. doi:10.2337/db10-0543
   PubMed Web of Science ®Google Scholar
• Ramos-Lopez O, Samblas M, Milagro FI, et al. Circadian gene methylation profiles are associated with obesity, metabolic disturbances and carbohydrate intake. Chronobiol Int. 2018;35:969–981. doi:10.1080/07420528.2018.1446021
   PubMed Web of Science ®Google Scholar
• Maruthur NM, Gribble MO, Bennett WL, et al. The pharmacogenetics of type 2 diabetes: a systematic review. Diabetes Care. 2014;37:876–886. doi:10.2337/dc13-1276
   PubMed Web of Science ®Google Scholar
• Porto AG, Brun F, Severini GM, et al. Clinical Spectrum of PRKAG2 Syndrome. Circ Arrhythm Electrophysiol. 2016;9:e003121. doi:10.1161/CIRCEP.115.003121
   Web of Science ®Google Scholar
• Luptak I, Shen M, He H, et al. Aberrant activation of AMP-activated protein kinase remodels metabolic network in favor of cardiac glycogen storage. J Clin Invest. 2007;117:1432–1439. doi:10.1172/JCI30658
   PubMed Web of Science ®Google Scholar
• Hunter RW, Treebak JT, Wojtaszewski JF, Sakamoto K. Molecular mechanism by which AMP-activated protein kinase activation promotes glycogen accumulation in muscle. Diabetes. 2011;60:766–774. doi:10.2337/db10-1148
   PubMed Web of Science ®Google Scholar
• Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE. Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. N Engl J Med. 1995;333:550–554. doi:10.1056/NEJM199508313330903
   PubMed Web of Science ®Google Scholar