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Erschienen in: International Journal of Diabetes in Developing Countries 4/2013

01.12.2013 | Original Article

Type 2 diabetes mellitus (T2DM) subjects of Bangladeshi origin with fast N-acetyltransferase 2 (NAT2) acetylator phenotype show lower insulin sensitivity than slow acetylator phenotype

verfasst von: Sudip Paul, Sohel Ahmed, Imran Khan, Zahid Hassan, Liaquat Ali

Erschienen in: International Journal of Diabetes in Developing Countries | Ausgabe 4/2013

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Abstract

Multiple genes may contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). N-acetyltransferase 2 (NAT2) is a phase II drug detoxifying enzyme for which susceptibility to the development of T2DM has been linked with its genetic polymorphisms. The role of polymorphisms in NAT2 gene in the development of T2DM among Bangladeshi population is not yet known. In the present study, to investigate whether NAT2 gene polymorphisms play a role in the susceptibility to T2DM, three common polymorphisms 481C>T, 590G>A, and 857G>A were investigated by PCR-RFLP method in 93 T2DM patients and 145 healthy controls of Bangladeshi origin. Our results indicate that none of the markers were associated with the increased risk of T2DM development in the studied population (P > 0.05). Although statistically insignificant (P = 0.259), fast acetylator type was higher in T2DM subjects than in control subjects (53.3 % vs. 45.7 %). T2DM subjects with fast acetylator type had significantly higher absolute insulin level and lower insulin sensitivity than that of slow acetylator type (P = 0.018 and P = 0.038 respectively), the biochemical and molecular basis of this variation needs to be studied further.
Literatur
1.
Zurück zum Zitat King H, Aubert RE, Herman WH. Global burden of diabetes 1995–2025: prevalence, numerical estimates and projections. Diabetes Care. 1998;21:1414–31.PubMedCrossRef King H, Aubert RE, Herman WH. Global burden of diabetes 1995–2025: prevalence, numerical estimates and projections. Diabetes Care. 1998;21:1414–31.PubMedCrossRef
2.
Zurück zum Zitat Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest. 1999;104:787–94.PubMedCentralPubMedCrossRef Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest. 1999;104:787–94.PubMedCentralPubMedCrossRef
3.
Zurück zum Zitat Zimmet P. Type 2 (noninsulin-dependent) diabetes: an epidemiological overview. Diabetologia. 1982;22:399–411.PubMedCrossRef Zimmet P. Type 2 (noninsulin-dependent) diabetes: an epidemiological overview. Diabetologia. 1982;22:399–411.PubMedCrossRef
4.
Zurück zum Zitat Lyssenko V, Jonsson A, Almgren P. Clinical risk factors, DNA variants, and the development of type 2 diabetes. N Engl J Med. 2008;359:2220–32.PubMedCrossRef Lyssenko V, Jonsson A, Almgren P. Clinical risk factors, DNA variants, and the development of type 2 diabetes. N Engl J Med. 2008;359:2220–32.PubMedCrossRef
5.
Zurück zum Zitat Hein DW, Doll MA, Rustan TD. Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and—polymorphic NAT2 acetyltransferases. Carcinogenesis. 1993;14:1633–8.PubMedCrossRef Hein DW, Doll MA, Rustan TD. Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and—polymorphic NAT2 acetyltransferases. Carcinogenesis. 1993;14:1633–8.PubMedCrossRef
6.
Zurück zum Zitat Hein DW, Doll MA, Fretland AJ. Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms. Cancer Epidemiol Biomarkers Prev. 2000;9:29–42.PubMed Hein DW, Doll MA, Fretland AJ. Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms. Cancer Epidemiol Biomarkers Prev. 2000;9:29–42.PubMed
7.
Zurück zum Zitat Hickman D, Risch A, Buckle V, Spurr N, Jeremiah SJ, McCarthy A, et al. Chromosomal localization of human genes for arylamine N-acetyltransferase. Biochem J. 1994;297:441–5.PubMed Hickman D, Risch A, Buckle V, Spurr N, Jeremiah SJ, McCarthy A, et al. Chromosomal localization of human genes for arylamine N-acetyltransferase. Biochem J. 1994;297:441–5.PubMed
8.
Zurück zum Zitat Windmill KF, Gaedigk A, Hall PM, Samaratunga H, Grant M, McManus ME. Localization of N-acetyltransferases NAT1 and NAT2 in human tissues. Toxicol Sci. 2000;54:19–29.PubMedCrossRef Windmill KF, Gaedigk A, Hall PM, Samaratunga H, Grant M, McManus ME. Localization of N-acetyltransferases NAT1 and NAT2 in human tissues. Toxicol Sci. 2000;54:19–29.PubMedCrossRef
9.
Zurück zum Zitat Anderson KE, Hammons GJ, Kadlubar FF, Potter JD, Kaderlik KR, Ileutt KF, et al. Metabolic activation of aromatic amines by human pancreas. Carcinogenesis. 1997;18:1085–92.PubMedCrossRef Anderson KE, Hammons GJ, Kadlubar FF, Potter JD, Kaderlik KR, Ileutt KF, et al. Metabolic activation of aromatic amines by human pancreas. Carcinogenesis. 1997;18:1085–92.PubMedCrossRef
10.
Zurück zum Zitat Butcher NJ, Boukouvala S, Sim E, Minchin RF. Pharmacogenetics of the arylamine N-acetyltransferases. Pharmacogenomics J. 2002;2:30–42.PubMedCrossRef Butcher NJ, Boukouvala S, Sim E, Minchin RF. Pharmacogenetics of the arylamine N-acetyltransferases. Pharmacogenomics J. 2002;2:30–42.PubMedCrossRef
11.
Zurück zum Zitat Blum M, Grant DM, McBride W, Heim M, Meyer UA. Human arylamine N-acetyltransferase genes: isolation, chromosomal localization, and functional expression. DNA Cell Biol. 1990;9:193–203.PubMedCrossRef Blum M, Grant DM, McBride W, Heim M, Meyer UA. Human arylamine N-acetyltransferase genes: isolation, chromosomal localization, and functional expression. DNA Cell Biol. 1990;9:193–203.PubMedCrossRef
12.
Zurück zum Zitat Weber WW, Hein DW. N-Acetylation pharmacogenetics. Pharmacol Rev. 1985;37:25–79.PubMed Weber WW, Hein DW. N-Acetylation pharmacogenetics. Pharmacol Rev. 1985;37:25–79.PubMed
13.
Zurück zum Zitat Evans DAP. N-acetyltransferase. In: Kalow W, editor. Pharmacogenetics of drug metabolism. New York: Pergamon Press; 1992. p. 95–178. Evans DAP. N-acetyltransferase. In: Kalow W, editor. Pharmacogenetics of drug metabolism. New York: Pergamon Press; 1992. p. 95–178.
14.
Zurück zum Zitat Hein DW, Ferguson RJ, Doll MA, Rustan TD, Gray K. Molecular genetics of human polymorphic N- acetyltransferase. Enzymatic analysis of 15 recombinant wildtype, mutant, and chimeric NAT2 allozymes. Hum Mol Genet. 1994;3:729–34.PubMedCrossRef Hein DW, Ferguson RJ, Doll MA, Rustan TD, Gray K. Molecular genetics of human polymorphic N- acetyltransferase. Enzymatic analysis of 15 recombinant wildtype, mutant, and chimeric NAT2 allozymes. Hum Mol Genet. 1994;3:729–34.PubMedCrossRef
15.
Zurück zum Zitat Bodansky HJ, Drury PL, Cudworth AG, Evans DAP. Acetylator phenotypes and type 1 (insulin-dependent) diabetics with microvascular disease. Diabetes. 1981;30:907–10.PubMedCrossRef Bodansky HJ, Drury PL, Cudworth AG, Evans DAP. Acetylator phenotypes and type 1 (insulin-dependent) diabetics with microvascular disease. Diabetes. 1981;30:907–10.PubMedCrossRef
16.
Zurück zum Zitat Korpinen E, Groop PH, Rautio A. N-acetyltransferase-2 polymorphism, smoking and type 1 diabetic nephropathy. Pharmacogenetics. 1999;9:627–33.PubMedCrossRef Korpinen E, Groop PH, Rautio A. N-acetyltransferase-2 polymorphism, smoking and type 1 diabetic nephropathy. Pharmacogenetics. 1999;9:627–33.PubMedCrossRef
17.
Zurück zum Zitat Agundez JA, Menaya JG, Tejeda R, Lago F, Chavez M, Benitez J. Genetic analysis of the NAT2 and CYP2D6 polymorphisms in white patients with non-insulin-dependent diabetes mellitus. Pharmacogenetics. 1996;6:465–72.PubMedCrossRef Agundez JA, Menaya JG, Tejeda R, Lago F, Chavez M, Benitez J. Genetic analysis of the NAT2 and CYP2D6 polymorphisms in white patients with non-insulin-dependent diabetes mellitus. Pharmacogenetics. 1996;6:465–72.PubMedCrossRef
18.
Zurück zum Zitat Hegele RA, Kwan K, Harris SB, Hanley AJ, Zinman B, Cao H. NAT2 polymorphism associated with plasma glucose concentration in Canadian Oji-Cree. Pharmacogenetics. 2000;10:233–8.PubMedCrossRef Hegele RA, Kwan K, Harris SB, Hanley AJ, Zinman B, Cao H. NAT2 polymorphism associated with plasma glucose concentration in Canadian Oji-Cree. Pharmacogenetics. 2000;10:233–8.PubMedCrossRef
19.
Zurück zum Zitat Yalin S, Hatungil R, Tamer L, Ates NA, Dogruer N, Yildirim H, et al. N-acetyltransferase 2 polymorphism in patients with diabetes mellitus. Cell Biochem Funct. 2007;25:407–11.PubMedCrossRef Yalin S, Hatungil R, Tamer L, Ates NA, Dogruer N, Yildirim H, et al. N-acetyltransferase 2 polymorphism in patients with diabetes mellitus. Cell Biochem Funct. 2007;25:407–11.PubMedCrossRef
21.
Zurück zum Zitat Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 1998;21:2191–2.PubMedCrossRef Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 1998;21:2191–2.PubMedCrossRef
22.
Zurück zum Zitat Inatomi H, Katoh K, Kawamoto T, Matsumoto T. NAT 2 gene polymorphism as a possible biomarker for susceptibility to bladder cancer in Japanese. Int J Urol. 1999;6:446–54.PubMedCrossRef Inatomi H, Katoh K, Kawamoto T, Matsumoto T. NAT 2 gene polymorphism as a possible biomarker for susceptibility to bladder cancer in Japanese. Int J Urol. 1999;6:446–54.PubMedCrossRef
23.
25.
Zurück zum Zitat Shenfield GM, McCann VJ, Tjokresetio R. Acetylator status and diabetic neuropathy. Diabetologia. 1982;22:441–4.PubMedCrossRef Shenfield GM, McCann VJ, Tjokresetio R. Acetylator status and diabetic neuropathy. Diabetologia. 1982;22:441–4.PubMedCrossRef
26.
Zurück zum Zitat Pontiroli AE, Mosca A, de Pasqua A, Alcini D, Pozza G. The fast acetylator phenotype in diabetes mellitus: abnormal prevalence and association with the ABO blood groups. Diabetologia. 1984;27:235–7.PubMed Pontiroli AE, Mosca A, de Pasqua A, Alcini D, Pozza G. The fast acetylator phenotype in diabetes mellitus: abnormal prevalence and association with the ABO blood groups. Diabetologia. 1984;27:235–7.PubMed
27.
Zurück zum Zitat Evans DAP, Paterson S, Fransisco P, Alvarege G. The acetylator phenotypes of Saudi Arabian diabetics. J Med Genet. 1985;22:479–83.PubMedCrossRef Evans DAP, Paterson S, Fransisco P, Alvarege G. The acetylator phenotypes of Saudi Arabian diabetics. J Med Genet. 1985;22:479–83.PubMedCrossRef
28.
Zurück zum Zitat Madacsy L, Szorady I, Santa A, Barkai L, Vamosi I. Association of microalbuminuria with slow acetylator phenotype in type 1 diabetes mellitus. Child Nephrol Urol. 1992;12:192–6.PubMed Madacsy L, Szorady I, Santa A, Barkai L, Vamosi I. Association of microalbuminuria with slow acetylator phenotype in type 1 diabetes mellitus. Child Nephrol Urol. 1992;12:192–6.PubMed
29.
Zurück zum Zitat Semiz S, Dujic T, Ostanek B, Velija-Asimi Z, Prnjavorac B, Bego T, et al. Association of NAT2 polymorphisms with type 2 diabetes in a population from Bosnia and Herzegovina. Arch Med Res. 2011;42:311–7.PubMedCrossRef Semiz S, Dujic T, Ostanek B, Velija-Asimi Z, Prnjavorac B, Bego T, et al. Association of NAT2 polymorphisms with type 2 diabetes in a population from Bosnia and Herzegovina. Arch Med Res. 2011;42:311–7.PubMedCrossRef
30.
Zurück zum Zitat Neugebauer S, Baba T, Watanabe T, Ishizaki T, Kurokawa K. The N-acetyltransferase (NAT) gene: an early risk marker for diabetic nephropathy in Japanese type 2 diabetic patients? Diabet Med. 1994;11:783–8.PubMedCrossRef Neugebauer S, Baba T, Watanabe T, Ishizaki T, Kurokawa K. The N-acetyltransferase (NAT) gene: an early risk marker for diabetic nephropathy in Japanese type 2 diabetic patients? Diabet Med. 1994;11:783–8.PubMedCrossRef
31.
Zurück zum Zitat Notkins AL. Immunologic and genetic factors in type 1 diabetes. Biol Chem. 2002;277:43545–8.CrossRef Notkins AL. Immunologic and genetic factors in type 1 diabetes. Biol Chem. 2002;277:43545–8.CrossRef
Metadaten
Titel
Type 2 diabetes mellitus (T2DM) subjects of Bangladeshi origin with fast N-acetyltransferase 2 (NAT2) acetylator phenotype show lower insulin sensitivity than slow acetylator phenotype
verfasst von
Sudip Paul
Sohel Ahmed
Imran Khan
Zahid Hassan
Liaquat Ali
Publikationsdatum
01.12.2013
Verlag
Springer India
Erschienen in
International Journal of Diabetes in Developing Countries / Ausgabe 4/2013
Print ISSN: 0973-3930
Elektronische ISSN: 1998-3832
DOI
https://doi.org/10.1007/s13410-013-0144-0

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