Association between the synonymous variant organic cation transporter 3 (OCT3)-1233G>A and the glycemic response following metformin therapy in patients with type 2 diabetes | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 3، دوره 20، شماره 3، خرداد 2017، صفحه 250-255 اصل مقاله (1.03 M) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2017.8351 | ||
| نویسندگان | ||
| Seyyedeh Raheleh Hosseyni-Talei1؛ Abdolkarim Mahrooz* 1، 2؛ Mohammad Bagher Hashemi-Soteh1؛ Maryam Ghaffari-Cherati1؛ Ahad Alizadeh3 | ||
| 1Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran | ||
| 2Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran | ||
| 3Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran | ||
| چکیده | ||
| Objective(s): Organic cation transporter 3 (OCT3) as a high-capacity transporter contribute to the metabolism of metformin. The present study was conducted to determine the genotype frequencies of the variant OCT3-1233G>A (rs2292334) in patients with newly diagnosed type 2 diabetes (T2D) and its relationship with response to metformin. Materials and Methods: This study included 150 patients with T2D who were classified into two groups following three months of metformin therapy: responders (by more than 1% reduction in HbA1c from baseline) and nonresponders (less than 1% reduction in HbA1c from baseline). PCR-based restriction fragment length polymorphism (RFLP) served to genotype OCT3-564G>A variant. Results: The parameters such as HbA1c (P<0.001) and BMI (P<0.001) in both patients with GA + AA genotype and GG genotype decreased significantly following 3 months of metformin therapy compared with baseline. The mean reduction in HbA1c levels following 3 months was higher in patients with the A allele (0.77% reduction from baseline) than in those with the homozygous G allele (0.54% reduction from baseline). Also, in GA + AA genotypes compared with GG genotypes, the mean reduction in HbA1c values from baseline was 0.34% for responders and 0.14% for non-responders. Conclusion: Considering the roles of genetic variations in the function of metformin transporters, the effect of variations such as 1233G>A in the OCT3, which is a high-capacity transporter widely expressed in various tissues cannot be ignored. Comparing the allele frequencies of OCT3-1233G>A variant in our study and different ethnic populations confirm that the variant is a highly polymorphic variant. | ||
| کلیدواژهها | ||
| HbA1c؛ Metformin؛ OCT3؛ Organic cation transporter 3؛ Type 2 diabetes | ||
| مراجع | ||
|
1.Weber MB, Narayan KV. Preventing type 2 diabetes: genes or lifestyle? Prim Care Diabetes 2008; 2:65–66.
2.Holstein A, Seeringer A, Kovacs P. Therapy with oral antidiabetic drugs: applied pharmacogenetics. Br J Diabetes Vasc Dis 2001; 11:10–16.
3.Goldenberg R, Punthakee Z. Definition, classification and diagnosis of diabetes, prediabetes and metabolic syndrome. Can J Diabetes 2013; 37; S8–S11.
4.Avery P, Mousa SS, Mousa SA. Pharmacogenomics in type II diabetes mellitus management: steps toward personalized medicine. Pharmgenomics Pers Med 2009; 2:79–91.
5.Standards of medical care in diabetes-2009. Diabet Care 2009; 32: S13–S61.
6.Mahrooz A, Parsanasab H, Hashemi-Soteh MB, Kashi Z, Bahar A, Alizadeh A, Mozayeni M. The role of clinical response to metformin in patients newly diagnosed with type 2 diabetes: a monotherapy study. Clin Exp Med 2015; 15: 159–165.
7.Kashi Z, Mahrooz A, Kianmehr A, Alizadeh A. The role of metformin response in lipid metabolism in patients with recent‑onset type 2 diabetes: HbA1c level as a criterion for designating patients as responders or nonresponders to metformin. PLoS One 2016; 11:e0151543.
8.Pacanowski MA, Hopley CW, Aquilante CL. Interindividual variability in oral antidiabetic drug disposition and response: the role of drug transporter polymorphisms. Expert Opin Drug MetabToxicol 2008; 4:529–544.
9.Gong Li, GoswamiSrijib, Giacomini KM, Altman RB, Klein TE. Metformin pathways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics 2012; 22:820–827.
10.Marchetti P, Scharp DW, Giannarelli R, Benzi L, Cicchetti P, Ciccarone AM, et al. Metformin potentiates glucose-stimulated insulin secretion. Diabet Care 1996; 19:781–782.
11.Robert F, Fendri S, Hary L, Lacroix C, Andréjak M, Lalau JD. Kinetics of plasma and erythrocyte metformin after acute administration in healthy subjects. Diabet Metab 2003; 29:279–283.
12.Kashi Z, Masoumi P, Mahrooz A, Hashemi-Soteh MB, Bahar A, Alizadeh A. The variant organic cation transporter 2 (OCT2)-T201M contribute to changes in insulin resistance in patients with type 2 diabetes treated with metformin. Diabetes Res Clin Pract 2015; 108:78–83.
13.Wu X, Huang W, Ganapathy ME, Wang H, Kekuda R, Conway SJ, et al. Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol 2000; 279:F449–458.
14.Chen L, Pawlikowski B, Schlessinger A, More SS, Stryke D, Johns SJ, et al. Role of organic cation transporter 3 (SLC22A3) and its missense variants in the pharmacologic action of metformin. Pharmacogenet Genomics 2010; 20:687–699.
15.Kerb R. Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett 2006; 234:4–33.
16.Lazar A, Grundemann D, Berkels R, Taubert D, Zimmermann T, Schömig E. Genetic variability of the extraneuronal monoamine transporter EMT (SLC22A3). J Hum Genet 2003; 48: 226-230.
17.Aoyama N, Takahashi N, Kitaichi K, Ishihara R, Saito S, Maeno N, et al. Association between gene polymorphisms of SLC22A3 and methamphetamine use disorder. Alcohol Clin Exp Res 2006; 30:1644–1649.
18.Todd JN, Florez JC. An update on the pharmacogenomics of metformin: progress, problems and potential. Pharmacogenomics 2014; 15:529–539.
19.Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18:499–502.
20.Hengen N, Lizer MH, Kidd RS. Evaluation of genetic variations in organic cationic transporter 3 in depressed and nondepressed subjects. ISRN Pharmacol 2011; 2011:161740.
21.Takane H, Shikata E, Otsubo K, Higuchi S, Ieiri I, et al. Polymorphism in human organic cation transporters and metformin action. Pharmacogenomics 2008; 9:415–422.
22.Becker ML, Visser LE, Van Schaik RH, Hofman A, Uitterlinden AG, Stricker BH. Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus. Pharmacogenomics J 2009; 9:242–247.
23.Nies AT, Koepsell H, Winter S, Burk O, Klein K, Kerb R, et al. Expression of organiccation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Hepatology 2009; 50:1227–1240.
24.Tzvetkov MV, Vormfelde SV, Balen D, Meineke I, Schmidt T, Sehrt D, et al. The effects of genetic polymorphisms in the organic cation transporters OCT1, OCT2, and OCT3 on the renal clearance of metformin. Clin Pharmacol Ther 2009; 86:299–306.
25.Wallace TM, Matthews DR. The assessment of insulin resistance in man. Diabet Med 2002; 19:527–534.
26.Rena G, Pearson ER, Sakamoto K. Molecular mechanism of action of metformin: old or new insights? Diabetologia 2013; 56:1898–1906.
27.Bosi E. Metformin – the gold standard in type 2 diabetes: what does the evidence tell us? Diabetes Obes Metab 2009; 11:3–8.
28.Abdul-Ghani MA, Puckett C, Triplitt C, Maggs D, Adams J, Cersosimo E, et al. Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. Results from the efficacy and durability of initial combination therapy for type 2 Diabetes (EDICT): a randomized trial. Diabetes Obes metab 2015; 17:268–275. | ||
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