Combined effect of oxidative stress-related gene polymorphisms on atherosclerosis

• Published in: Biochemical and Biophysical Research Communications Vol. 379; no. 4; pp. 861 - 865
• Main Authors: Katakami, N., Sakamoto, K., Kaneto, H., Matsuhisa, M., Shimizu, I., Ishibashi, F., Osonoi, T., Kashiwagi, A., Kawamori, R., Hori, M., Yamasaki, Y.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.02.2009; Elsevier BV
• Subjects: Alleles; Aryldialkylphosphatase; Aryldialkylphosphatase - genetics; Atherosclerosis; Atherosclerosis - complications; Atherosclerosis - genetics; Atherosclerosis - pathology; Carotid Arteries; Carotid Arteries - pathology; Carotid Artery Diseases; Carotid Artery Diseases - complications; Carotid Artery Diseases - genetics; Carotid Artery Diseases - pathology; Diabetes; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - enzymology; Female; Genetic Predisposition to Disease; Glutamate-Cysteine Ligase; Glutamate-Cysteine Ligase - genetics; Humans; IMT; Male; Oxidative Stress; Oxidative Stress - genetics; Peroxidase; Peroxidase - genetics; Polymorphism; Polymorphism, Genetic; Tunica Intima; Tunica Intima - pathology; Oxidative stress; IMT; Diabetes; Atherosclerosis; Polymorphism
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2008.12.154

It is well known that oxidative stress plays critical roles in the pathogenesis of atherosclerosis. In this study, we enrolled 1746 type 2 diabetic subjects, determined 4 common genetic variants related to oxidative stress ( glutamate-cysteine ligase modifier subunit (GCLM) C-588T, myeloperoxidase G-463A, human paraoxonase 1 Gln192Arg and NAD(P)H oxidase p22phox C242T polymorphisms), and measured carotid intima-media thickness (IMT) as a surrogate marker for atherosclerosis. GCLM C-588T polymorphism was associated with average IMT (AveIMT) ( r = 0.090, p = 0.0008), but the association between the other 3 polymorphisms and AveIMT did not reach the statistical significance. However, AveIMT was significantly greater as the total number of 4 concomitant “pro-oxidant alleles” in each subject was increased ( r = 0.108, p < 0.0001). Furthermore, the number of “pro-oxidant alleles” was a risk factor for a high AveIMT independently of conventional risk factors ( p = 0.0003). In conclusion, accumulation of oxidative stress-associated alleles was associated with carotid atherosclerosis in type 2 diabetic patients.