Association of NAD(P)H Oxidase p22 phox Gene Variation With Advanced Carotid Atherosclerosis in Japanese Type 2 Diabetes
- Rieko Hayaishi-Okano, MD, PHD,
- Yoshimitsu Yamasaki, MD, PHD,
- Yoshitaka Kajimoto, MD, PHD,
- Ken’ya Sakamoto, MD, PHD,
- Kentaro Ohtoshi, MD,
- Naoto Katakami, MD,
- Dan Kawamori, MD,
- Takeshi Miyatsuka, MD,
- Masahiro Hatazaki, MD,
- Yoji Hazama, MD and
- Masatsugu Hori, MD, PHD
- Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Yamadaoka Suita City, Osaka, Japan
Abstract
OBJECTIVE—To evaluate the association between the C242T polymorphism of the p22 phox gene, an essential component of NAD(P)H oxidase in the vasculature, with intima-media thickness (IMT) of the carotid artery and risk factors for atherosclerosis in type 2 diabetic subjects.
RESEARCH DESIGN AND METHODS—C242T polymorphism of the p22 phox gene was detected by polymerase chain reaction-restriction fragment-length polymorphism in 200 Japanese type 2 diabetic subjects and 215 nondiabetic subjects. We examined the association with this mutation and carotid atherosclerosis as well as the patients’ clinical characteristics and the level of 8-hydroxy-2′deoxyguanosine (8-OHdG) as an index of oxidative DNA damage.
RESULTS—The diabetic subjects with the TC+TT genotypes displayed a significantly lower average IMT (1.13 ± 0.31 vs. 1.31 ± 0.34 mm; P = 0.0099) and a not significantly lower serum 8-OHdG level than those with the CC genotype, despite no difference in the risk factors. Stepwise multiple regression analysis showed that the risk factors for increased IMT in the diabetic subjects were systolic blood pressure (P = 0.0042) and p22 phox CC genotype (P = 0.0151). In nondiabetic subjects, the average IMT of the TC+TT group was not different from that of the CC group (0.85 ± 0.14 vs. 0.94 ± 0.30 mm, P = 0.417). Fasting plasma insulin concentration (41.4 ± 15.6 vs. 64.2 ± 59.4 pmol/l, P = 0.0098) and insulin resistance index of homeostasis model assessment (HOMA-R) (1.58 ± 0.66 vs. 2.60 ± 2.56, P = 0.0066) were significantly lower in the TC+TT group than in the CC group.
CONCLUSIONS—These results show that the C242T mutation in the p22 phox gene is associated with progression of asymptomatic atherosclerosis in the subjects with type 2 diabetes and is also associated with insulin resistance in nondiabetic subjects.
- 8-OHdG, 8-hydroxy-2′deoxyguanosine
- CHD, coronary heart disease
- HOMA-R, insulin resistance index of homeostasis model assessment
- IMT, intima-media thickness
- ROS, reactive oxygen species
Footnotes
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Address correspondence and reprint requests to Yoshimitsu Yamasaki, MD, PhD, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2–2, Yamadaoka Suita City, Osaka 565-0871, Japan. E-mail; yamasaki{at}medone.med.osaka-u.ac.jp.
Received for publication 9 June 2002 and accepted in revised form 30 September 2002.
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