Abstract
Aim:
The aim of the present study was to investigate the relationship between R219K, M883I, and R1587K variants of the ATP-binding cassette transporter subfamily A number 1 (ABCA1) gene and response to rosiglitazone treatment in newly diagnosed patients with type 2 diabetes.
Methods:
A total of 105 diabetic patients with no history of antihyperglycemia medication were treated with rosiglitazone (4 or 8 mg daily) for 48 weeks. Three non-synonymous variants R219K, M883I, and R1587K, were genotyped in all patients.
Results:
Ninety-three patients completed the entire study. The R219K variant of ABCA1 had an effect on rosiglitazone response with the per-allele odds ratio of 2.04 for treatment failure (P < 0.05). The RR homozygotes had a better improvement in indicators of insulin sensitivity, as determined by a significantly greater decrease in the homeostasis model assessment index of insulin resistance (-2.39±0.46 vs -0.69±0.51, P < 0.05). No genotype-phenotype association was detected for M883I and R1587K.
Conclusion:
The R219K variant of ABCA1 was associated with the therapeutic effect of rosiglitazone. The RR homozygotes had a better response to rosiglitazone treatment in terms of insulin sensitivity improvement than minor K allele carriers. Neither the M883I nor R1587K variant of the ABCA1 gene was associated with rosiglitazone response.
Similar content being viewed by others
Article PDF
References
Stumvoll M, Goldstein BJ, van Haeften TW . Type 2 diabetes: principles of pathogenesis and therapy. Lancet 2005; 365: 1333–46.
DeFronzo RA . Pathogenesis of type 2 (non-insulin dependent) diabetes mellitus: a balanced overview. Diabetologia 1992; 35: 389–97.
Elte JW, Blickle JF . Thiazolidinediones for the treatment of type 2 diabetes. Eur J Intern Med 2007; 18: 18–25.
Rosen ED, Spiegelman BM . PPARγ: a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem 2001; 276: 37731–4.
Day C . Thiazolidinediones: a new class of antidiabetic drugs. Diabet Med 1999; 16: 179–92.
Buchanan TA, Xiang AH, Peters RK, Kjos SL, Marroquin A, Goico J, et al. Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women. Diabetes 2002; 51: 2796–803.
Eichelbaum M, Ingelman-Sundberg M, Evans WE . Pharmacogenomics and individualized drug therapy. Annu Rev Med 2006; 57: 119–37.
Kirchheiner J, Thomas S, Bauer S, Tomalik-Scharte D, Hering U, Doroshyenko O, et al. Pharmacokinetics and pharmacodynamics of rosiglitazone in relation to CYP2C8 genotype. Clin Pharmacol Ther 2006; 80: 657–67.
Kang ES, Park SY, Kim HJ, Ahn CW, Nam M, Cha BS, et al. The influence of adiponectin gene polymorphism on the rosiglitazone response in patients with type 2 diabetes. Diabetes Care 2005; 28: 1139–44.
Snitker S, Watanabe RM, Ani I, Xiang AH, Marroquin A, Ochoa C, et al. Changes in insulin sensitivity in response to troglitazone do not differ between subjects with and without the common, functional Pro12Ala peroxisome proliferator-activated receptor-γ2 gene variant: results from the troglitazone in Prevention of Diabetes (TRIPOD) study. Diabetes Care 2004; 27: 1365–8.
Bluher M, Lubben G, Paschke R . Analysis of the relationship between the Pro12Ala variant in the PPAR-gamma2 gene and the response rate to therapy with pioglitazone in patients with type 2 diabetes. Diabetes Care 2003; 26: 825–31.
Wolford JK, Yeatts KA, Dhanjal SK, Black MH, Xiang AH, Buchanan TA, et al. Sequence variation in PPARG may underlie differential response to troglitazone. Diabetes 2005; 54: 3319–25.
Kang ES, Park S Y, Kim HJ, Kim CS, Ahn CW, Cha BS, et al. Effects of Pro12Ala polymorphism of peroxisome proliferator-activated receptor γ2 gene on rosiglitazone response in type 2 diabetes. Clin Pharmacol Ther 2005; 78: 202–8.
Florez JC, Jablonski KA, Sun MW, Bayley N, Kahn SE, Shamoon H, et al. Effects of the type 2 diabetes-associated PPARG P12A polymorphism on progression to diabetes and response to troglitazone. J Clin Endocrinol Metab 2007; 92: 1502–9.
Attie AD . ABCA1: at the nexus of cholesterol, HDL and atherosclerosis. Trends Biochem Sci 2007; 32: 172–9.
Daimon M, Ji G, Saitoh T, Oizumi T, Tominaga M, Nakamura T, et al. Large-scale search of SNPs for type 2 DM susceptibility genes in a Japanese population. Biochem Biophys Res Commun 2003; 302: 751–8.
Daimon M, Kido T, Baba M, Oizumi T, Jimbu Y, Kameda W, et al. Association of the ABCA1 gene polymorphisms with type 2 DM in a Japanese population. Biochem Biophys Res Commun 2005; 329: 205–10.
Brunham LR, Kruit JK, Pape TD, Timmins JM, Reuwer AQ, Vasanji Z, et al. Beta-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatment. Nat Med 2007; 13: 340–7.
Alberti KG, Zimmet PZ . Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998; 15: 539–53.
Matthews DR, Hosker J P, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–9.
Scheen AJ, Lefebvre PJ . Troglitazone: antihyperglycemic activity and potential role in the treatment of type 2 diabetes. Diabetes Care 1999; 22: 1568–77.
Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355: 2427–43.
Rosenstock J, Baron MA, Dejager S, Mills D, Schweizer A . Comparison of vildagliptin and rosiglitazone monotherapy in patients with type 2 diabetes: a 24-week, double-blind, randomized trial. Diabetes Care 2007; 30: 217–23.
Wigginton JE, Cutler DJ, Abecasis GR . A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet 2005; 76: 887–93.
Barrett JC, Fry B, Maller J, Daly MJ . Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21: 263–5.
Weinshilboum RM, Wang L . Pharmacogenetics and pharmacogenomics: development, science, and translation. Annu Rev Genomics Hum Genet 2006; 7: 223–45.
Gerstein HC, Yusuf S, Bosch J, Pogue J, Sheridan P, Dinccag N, et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006; 368: 1096–105.
Chawla A, Boisvert WA, Lee CH, Laffitte BA, Barak Y, Joseph SB, et al. A PPARγ-LXR–ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell 2001; 7: 161–71.
Chinetti G, Lestavel S, Bocher V, Remaley AT, Neve B, Torra I P, et al. PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med 2001; 7: 53–8.
Unger RH . Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications. Diabetes 1995; 44: 863–70.
Robertson RP, Harmon J, Tran PO, Poitout V . Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes 2004; 53 Suppl 1: S119–24.
Poitout V, Robertson RP . Mini review: secondary beta-cell failure in type 2 diabetes—a convergence of glucotoxicity and lipotoxicity. Endocrinology 2002; 143: 339–42.
Clee SM, Zwinderman AH, Engert JC, Zwarts KY, Molhuizen HO, Roomp K, et al. Common genetic variation in ABCA1 is associated with altered lipoprotein levels and a modified risk for coronary artery disease. Circulation 2001; 103: 1198–205.
Soro-Paavonen A, Naukkarinen J, Lee-Rueckert M, Watanabe H, Rantala E, Soderlund S, et al. Common ABCA1 variants, HDL levels, and cellular cholesterol efflux in subjects with familial low HDL. J Lipid Res 2007; 48: 1409–16.
Evans D, Beil FU . The association of the R219K polymorphism in the ATP-binding cassette transporter 1 (ABCA1) gene with coronary heart disease and hyperlipidaemia. J Mol Med 2003; 81: 264–70.
Brunham LR, Singaraja RR, Pape TD, Kejariwal A, Thomas PD, Hayden MR . Accurate prediction of the functional significance of single nucleotide polymorphisms and mutations in the ABCA1 gene. PLoS Genet 2005; 1: e83.
Frikke-Schmidt R, Nordestgaard BG, Jensen GB, Tybjaerg-Hansen A . Genetic variation in ABC transporter A1 contributes to HDL cholesterol in the general population. J Clin Invest 2004; 114: 1343–53.
Author information
Authors and Affiliations
Corresponding author
Additional information
Project supported by the National 973 Program (No 2006CB503901) and the Key Project of the Science and Technology Commission of Shanghai Municipality (No 01ZD002).
Rights and permissions
About this article
Cite this article
Wang, J., Bao, Yq., Hu, C. et al. Effects of ABCA1 variants on rosiglitazone monotherapy in newly diagnosed type 2 diabetes patients. Acta Pharmacol Sin 29, 252–258 (2008). https://doi.org/10.1111/j.1745-7254.2008.00744.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2008.00744.x
Keywords
This article is cited by
-
Genetic polymorphisms in ABCA1 (rs2230806 and rs1800977) and LIPC (rs2070895) genes and their association with the risk of type 2 diabetes: a case control study
International Journal of Diabetes in Developing Countries (2022)
-
Characteristics of movable fluids in tight sandstone reservoir and its influencing factors: a case study of Chang 7 reservoir in the Southwestern of Ordos Basin
Journal of Petroleum Exploration and Production Technology (2021)
-
Joint effects of diabetic-related genomic loci on the therapeutic efficacy of oral anti-diabetic drugs in Chinese type 2 diabetes patients
Scientific Reports (2016)
-
Pharmacogenetics and personalized treatment of type 2 diabetes mellitus
International Journal of Diabetes in Developing Countries (2016)
-
A variant of PSMD6 is associated with the therapeutic efficacy of oral antidiabetic drugs in Chinese type 2 diabetes patients
Scientific Reports (2015)