ABSTRACT
Glutathione S-transferase (GST) plays a key role in the detoxification of xenobiotic atherogen generated by smoking. To analyze the effect of GSTM1/T1 gene polymorphisms on the development of smoking-related coronary artery disease (CAD), 775 Korean patients who underwent coronary angiography were enrolled. The subjects were classified by luminal diameter stenosis into group A (>50%), B (20-50%), or C (<20%). GSTM1 and GSTT1 gene polymorphisms were analyzed using multiplex polymerase chain reaction (PCR) for GSTM1/T1 genes and CYP1A1 gene for internal control. Of 775 subjects, 403 patients belonged to group A. They had higher risk factors for CAD than group B (N=260) and group C (N=112). The genotype frequencies of null GSTM1 and GSTT1 showed no significant differences among 3 groups. Considering the effect of GSTM1 gene polymorphisms on the smoking-related CAD, smokers with GSTM1 null genotype had more increased risk for CAD than non-smoker with GSTM1 positive genotype (odds ratios [OR], 2.07, confidence interval [CI], 1.06-4.07). Also the effect of GSTT1 gene polymorphism on smoking-related CAD showed the same tendency as GSTM1 gene (OR, 2.00, CI, 1.05-3.84). This effect of GSTM1/T1 null genotype on smoking-related CAD was augmented when both gene polymorphisms were considered simultaneously (OR, 2.76, CI, 1.17-6.52). We concluded that GSTM1/T1 null genotype contributed to the pathogenesis of smoking-related CAD to some degree.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Coronary Angiography , Coronary Artery Disease/epidemiology , Genetic Predisposition to Disease/epidemiology , Genotype , Glutathione Transferase/genetics , Polymorphism, Genetic , Risk Factors , Severity of Illness Index , Smoking/epidemiologyABSTRACT
BACKGROUND: It has been hypothesized that early atherosclerosis may be related to the pathogenesis of coronary vasospasm. This study was designed to investigate the relationship between early atherosclersosis and coronary vasospasm or vasoconstriction in response to axetylcholine utilizing intravascular ultrasonography. METHOD: Total 43 segments were analyzed from subjects who were composed of 10 patients with and 7 patients without coronary vasospasm in response to intra coronary acetylcholine infusion. Spasm segment(Sp) was defined as total or subtotal occlusion, constriction segment(C) as diameter decrease>/=10%, and normal segment(N) as diameter decrease 0.5mm. RESULTS: The atherosclerotic plaques of spasm segments were significantly thicker than those of normal and constriction segments(spasm segments : 1.19+/-0.21mm, constrict segments : 0.58+/-0.11mm, normal segment : 0.37+/-0.11, p<0.05). Atherosclerosis was present in 90% of spasm segments. Among normal of constriction segments, atherosclerotic plaque thickness of patients with vasospasm was thicker than that of patients without vasospasm, although it was statistically insignificant(patients with vasospasm : 0.65+/-0.51mm, patients without vasospasm 0.36+/-0.39mm, p=0.07). Frequency of atherosclerosis in normal or constriction segments was significantly higher in patients with vasospasm than patients without vasospasm(patients with vasospasm 47%, patients without vasospasm : 11%, p<0.05). CONCLUSION: Atherosclerosis is present at segments of vasospasm in response to intracoronary acetylcholine. Even among normal or constriction segments, the artherosclerotic plaque thickness of patients with vasospasm was thicker than that of patients without vasospasm which may indicates that coronary vasospasm is a diffuse early atherosclerotic disease.