The C609T variant of NQ01 is associated with carotid artery plaques in patients with type 2 diabetes

被引:24
作者
Han, Seung Jin [2 ,3 ]
Kang, Eun Seok [1 ,4 ]
Kim, Hyeong Jin [5 ]
Kim, So Hun
Chun, Sung Wan [1 ]
Ahn, Chul Woo [1 ,4 ]
Cha, Bong Soo [1 ,4 ]
Nam, Moonsuk [6 ]
Lee, Hyun Chul [1 ,3 ,4 ]
机构
[1] Yonsei Univ, Coll Med, Div Endocrinol & Metab, Dept Internal Med, Seoul, South Korea
[2] Ajou Univ, Sch Med, Dept Endocrinol & Metab, Suwon 441749, South Korea
[3] Yonsei Univ, Grad Sch, Dept Med, Seoul 120749, South Korea
[4] Yonsei Univ, Coll Med, Brain Korea Med Sci 21, Seoul 120749, South Korea
[5] Kwandong Univ, Myongii Hosp, Coll Med, Dept Internal Med, Koyang, South Africa
[6] Inha Univ, Coll Med, Dept Internal Med, Inchon, South Korea
关键词
Carotid atherosclerosis; Carotid artery plaque; NQO1; SNP; Type; 2; diabetes; INTIMA-MEDIA THICKNESS; NAD(P)H-QUINONE OXIDOREDUCTASE-1; ENDOTHELIAL-CELLS; GENE; POLYMORPHISM; ATHEROSCLEROSIS; NAD(P)H; COMPLICATIONS; SENSITIVITY; EXPRESSION;
D O I
10.1016/j.ymgme.2009.01.012
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Atherosclerosis in patients with type 2 diabetes has been linked to oxidative stress. NADP[1]:quinone oxidoreductase 1 (NQO1) plays a key role in cellular antioxidant defense. Recent reports suggest that highly expressed and inducible enclogenous NQO1 from cardiovascular cells may act as a potential superoxide scavenger. We examined the relationship between the risk of NQO1 C609T polymorphism and carotid artery atherosclerosis in patients with type 2 diabetes. Methods: We recruited 601 (Seoul set) and 233 (Koyang set) unrelated patients with type 2 diabetes from independent groups. The C609T variant of NQO1 was genotyped by Taqman RT-PCR. Mean and maximum carotid intima-media thickness (IMT) and carotid artery plaques were measured by high-resolution ultrasonography. Results: Patients with the T allele exhibited a higher prevalence of atherosclerotic plaques than non-T allele carriers in both sets (Seoul set vs. Koyang set, p = 0.02 1, p = 0.023, respectively). After adjusting for age, sex, duration of diabetes, systolic blood pressure, body mass index, current smoking, HDL-cholesterol, LDL-cholesterol and HbA1c, subjects with the T allele had a significantly higher risk of carotid artery plaques (Seoul set vs. Koyang set, OR = 1.65, p = 0.015: OR = 2.00, p = 0.037, respectively) than subjects with the CC genotype. Conclusion: These results suggest that the C609T polymorphism of NQO1 is associated with carotid artery plaques in type 2 diabetic patients. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:85 / 90
页数:6
相关论文
共 31 条
[1]   Genetic variation in PPARG encoding peroxisome proliferator-activated receptor γ associated with carotid atherosclerosis [J].
Al-Shali, KZ ;
House, AA ;
Hanley, AJG ;
Khan, HMR ;
Harris, SB ;
Zinman, B ;
Mamakeesick, M ;
Fenster, A ;
Spence, JD ;
Hegele, RA .
STROKE, 2004, 35 (09) :2036-2040
[2]   The pathobiology of diabetic complications - A unifying mechanism [J].
Brownlee, M .
DIABETES, 2005, 54 (06) :1615-1625
[3]   Polymorphisms in the angiotensinogen gene are associated with carotid intimal-medial thickening in females from a community-based population [J].
Chapman, CML ;
Palmer, LJ ;
McQuillan, BM ;
Hung, J ;
Burley, J ;
Hunt, C ;
Thompson, PL ;
Beilby, JP .
ATHEROSCLEROSIS, 2001, 159 (01) :209-217
[4]   Activation of Nrf2/ARE pathway protects endothelial cells from oxidant injury and inhibits inflammatory gene expression [J].
Chen, XL ;
Dodd, G ;
Thomas, S ;
Zhang, XL ;
Wasserman, MA ;
Rovin, BH ;
Kunsch, C .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2006, 290 (05) :H1862-H1870
[5]   Laminar flow induction of antioxidant response element-mediated genes in endothelial cells - A novel anti-inflammatory mechanism [J].
Chen, XL ;
Varner, SE ;
Rao, AS ;
Grey, JY ;
Thomas, S ;
Cook, CK ;
Wasserman, MA ;
Medford, RM ;
Jaiswal, AK ;
Kunsch, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (02) :703-711
[6]   Flow, NO, and atherogenesis [J].
Cooke, JP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (03) :768-770
[7]   NAD(P)H:quinone oxidoreductase:: polymorphisms and allele frequencies in Caucasian, Chinese and Canadian Native Indian and Inuit populations [J].
Gaedigk, A ;
Tyndale, RF ;
Jurima-Romet, M ;
Sellers, EM ;
Grant, DM ;
Leeder, JM .
PHARMACOGENETICS, 1998, 8 (04) :305-313
[8]  
Gavin JR, 1997, DIABETES CARE, V20, P1183
[9]   The pathogenesis of atherosclerosis [J].
Hegele, RA .
CLINICA CHIMICA ACTA, 1996, 246 (1-2) :21-38
[10]   Disparate associations of a functional promoter polymorphism in PCK1 with carotid wall ultrasound traits [J].
Hegele, RA ;
Al-Shali, KZ ;
House, AA ;
Hanley, AJG ;
Harris, SB ;
Mamakeesick, M ;
Fenster, A ;
Zinman, B ;
Cao, HN ;
Spence, JD .
STROKE, 2005, 36 (12) :2566-2570