| Korean Diabetes J. 2009 Feb;33(1):24-30. Korean. Published online February 28, 2009. https://doi.org/10.4093/kdj.2009.33.1.24 | |
| Copyright © 2009 Korean Diabetes Association | |
Dohee Kim
| |
| Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea. | |
|
| |
| Received February 02, 2009; Accepted February 14, 2009. | |
|
Abstract
| |
|
Background
NAD(P)H: quinone oxidoreductase 1 (NQO1), which is an obligate two-electron reductase that utilizes NAD(P)H as an electron donor and is involved in the protection against oxidative stress, is likely involved in β-cell destruction. We evaluated the frequency of the NQO1 polymorphism and its association with blood glucose levels.
Methods
Genotypes were determined using a polymerase chain reaction restriction fragment length polymorphism-based assay in 56 patients and 48 healthy subjects. Fasting blood glucose, insulin, and lipid profiles were measured and homeostasis model assessment (HOMA)-insulin resistance (IR) was calculated from fasting glucose and insulin levels in the healthy subjects.
Results
The genotype frequencies of NQO1 polymorphism were C/C (56.7%), C/T (42.3%), and T/T (1.0%). There were no associations between the NQO1 polymorphism and body mass index, blood pressure, lipid profile, HbA1c, postprandial glucose, and HOMA-IR. However, NQO1 mutants (C/T and T/T) showed weak but significantly higher fasting blood glucose levels compared with wild type (C/C).
Conclusion
Our data suggest that NQO1 609 C → T polymorphism may be associated with glucose metabolism. |
|
Keywords: Blood glucose; Human NQO1; Single nucleotide polymorphism |
|
|
Figures
|
|
|
Tables
|
|
|
|
References
|
| 1. | West IC. Radicals and oxidative stress in diabetes. Diabet Med 2000;17:171–180. 
|
| 2. | Kim SS, Son SM. Oxidative stress and cell dysfunction in diabetes: role of ROS produced by mitochondria and NAD(P)H oxidase. Korean Diabetes J 2008;32:389–398.  
|
| 3. | Robertson RP, Harmon J, Tran PO, Tanaka Y, Takahashi H. Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes 2003;52:581–587.
|
| 4. | Ross D, Kepa JK, Winski SL, Beall HD, Anwar A, Siegel D. NAD(P)H:quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms. Chem Biol Interact 2000;129:77–97.
|
| 5. | Joseph P, Xie T, Xu Y, Jaiswal AK. NAD(P)H: quinone oxidoreductase1 (DT-diaphorase): expression, regulation, and role in cancer. Oncol Res 1994;6:525–532.
|
| 6. | Gaikwad A, Long DJ 2nd, Stringer JL, Jaiswal AK. In vivo role of NAD(P)H:quinone oxidoreductase 1 (NQO1) in the regulation of intracellular redox state and accumulation of abdominal adipose tissue. J Biol Chem 2001;276:22559–22564.
|
| 7. | Palming J, Sjöholm K, Jernås M, Lystig TC, Gummesson A, Romeo S, Lönn L, Lönn M, Carlsson B, Carlsson LM. The expression of NAD(P)H:quinone oxidoreductase 1 is high in human adipose tissue, reduced by weight loss, and correlates with adiposity, insulin sensitivity, and markers of liver dysfunction. J Clin Endocrinol Metab 2007;92:2346–2352.
|
| 8. | Kelsey KT, Wiencke JK, Christiani DC, Zuo Z, Spitz MR, Xu X, Lee BK, Schwartz BS, Traver RD, Ross D. Ethnic variation in the prevalence of a common NAD(P)H:quinone oxidoreductase polymorphism and its implications for anticancer chemotherapy. Br J Cancer 1997;76:852–854.
|
| 9. | Hirai M, Suzuki S, Kasuga S, Chiba M, Toyota T. Association of DT-diaphorase Pro187Ser mutation with insulin-dependent diabetes mellitus in Japan. Diabetes 1998;47 suppl 1:S696. |
| 10. | Kristiansen OP, Larsen ZM, Johannesen J, Nerup J, Mandrup-Poulsen T, Pociot F. DIEGG and DSGD; Danish IDDM epidemiology and genetics group and the Danish Study Group of Diabetes in Childhood. No linkage of P187S polymorphism in NAD(P)H: quinone oxidoreductase (NQO1/DIA4) and type 1 diabetes in the Danish population. Hum Mutat 1999;14:67–70.
|
| 11. | Wang G, Zhang L, Li Q. Genetic polymorphisms of GSTT1, GSTM1, and NQO1 genes and diabetes mellitus risk in Chinese population. Biochem Biophys Res Commun 2006;341:310–313.
|
| 12. | Eickelmann P, Schulz WA, Rohde D, Schmitzdrager B, Sies H. Loss of heterozygosity at the NAD(P)H-quinone oxidoreductase locus associated with increased resistance against mitomycin C in a human bladder carcinoma cell line. Biol Chem Hoppe-Seyle 1994;375:439–445. |
| 13. | Siegel D, McGuinness SM, Winski SL, Ross D. Genotype-phenotype relationships in studies of a polymorphism in NAD(P)H:quinone oxidoreductase 1. Pharmacogenetics 1999;9:113–121.
|
| 14. | Sjöström L, Larsson B, Backman L, Bengtsson C, Bouchard C, Dahlgren S, Hallgren P, Jonsson E, Karlsson J, Lapidus L, Lindroos A-K, Lindstedt S, Lissner L, Narbro K, Näslund I, Olbe L, Sullivan M, Sylvan A, Wedel H, Ågren G. Swedish obese subjects (SOS). Recruitment for an intervention study and a selected description of the obese state. Int J Obes Relat Metab Disord 1992;16:465–479. |
| 15. | Berg CM, Lissner L, Aires N, Lappas G, Toren K, Wilhelmsen L, Rosengren A, Thelle DS. Trends in blood lipid levels, blood pressure, alcohol and smoking habits from 1985 to 2002: results from INTERGENE and GOTMONICA. Eur J Cardiovasc Prev Rehabil 2005;12:115–125.
|
| 16. | Gaedigk A, Tyndale RF, Jurima-Romet M, Sellers EM, Grant DM, Leeder JS. NAD(P)H:quinone oxidoreductase; polymorphisms and allele frequencies in Caucasian, Chinese and Canadian Native Indian and Inuit populations. Pharmacogenetics 1998;8:305–313.
|
| 17. | Victor RG, Haley RW, Willett DL, Peshock RM, Vaeth PC, Leonard D, Basit M, Cooper RS, Iannacchione VG, Visscher WA, Staab JM, Hobbs HH. The Dallas Heart Study: a population-based probability sample for the multidisciplinary study of ethnic differences in cardiovascular health. Am J Cardiol 2004;93:1473–1480.
|
An Association between 609 C → T Polymorphism in NAD(P)H: Quinone Oxidoreductase 1 (NQO1) Gene and Blood Glucose Levels in Korean Population
