Combined effect of oxidative stress-related gene polymorphisms on atherosclerosis.
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.
Katakami
N
N
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan. katakami@medone.med.osaka-u.ac.jp
Sakamoto
K
K
Kaneto
H
H
Matsuhisa
M
M
Shimizu
I
I
Ishibashi
F
F
Osonoi
T
T
Kashiwagi
A
A
Kawamori
R
R
Hori
M
M
Yamasaki
Y
Y
D000483:Alleles; D043303:Aryldialkylphosphatase / Q000235:genetics; D050197:Atherosclerosis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology; D002340:Carotid Artery Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000201:enzymology; D005260:Female; D020022:Genetic Predisposition to Disease; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000235:genetics*; D009195:Peroxidase / Q000235:genetics; D011110:Polymorphism, Genetic; D017539:Tunica Intima / Q000473:pathology
D009195:Peroxidase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D005721:Glutamate-Cysteine Ligase