| 황석재¹, 윤성은 ¹ , 권태정¹ , 박정랑¹ , 박용휘¹ , 정영훈¹ , 김인숙² , 곽충환¹ , 황진용¹ |
Background: The pathogenesis of coronary artery disease(CAD) in young women with lower burden of atherosclerosis risk factors has not been fully elucidated yet. Oxidative stress plays a key role in the pathophysiology of CAD behind the conventional risk factors such as hypertension, diabetes and the metabolic syndrome. The aim of this study was to assess whether the deletion mutation of antioxidant enzymes, glutathione S-transferase (GST) was associated with risk of CAD in young women compared to men. Method: We genotyped 655 CAD patients for GST T1 and M1 deletion by multiplex polymerase chain reaction. CAD was diagnosed if there was over 50% obstruction of one or more major coronary vessels. Since the increased burden of conventional risk factors in women after 65 years old, the impact of GST deletion mutation on the risk of CAD according to sex was analyzed in patient groups, above and below 65 years old respectively. Results: Among the CAD patients below 65 years old (n=376), female patients was older (58 ± 7 vs. 55 ± 7, P < 0.001) and male patients had more hypertension (58.0% vs. 36.1%, P < 0.001) and current smoker was more frequent in men (56.3% vs. 15.7%, P < 0.001) but the frequencies of diabetes was not different. The absence of GST T1 (null genotype) was markedly more frequent in women than men, 73.5% (61/83) vs. 50.9% (149/293) (P < 0.001). But the frequency of GST M1 null genotype was not different between men and women, 56.6% (47/83) vs. 58.7% (172/293) (P = 0.801). In a multivariate analysis (covariate: age, hypertension, current smoking, diabetes and GST T1 null genotype), GST T1 null genotype was independently associated with CAD in female patients, below 65 years old (adjusted odd ratio: 2.72, 95% confidence interval: 1.52-4.87). Among the CAD patients above 65 years old (n=279), female patients was older (75 ± 5 vs. 72 ± 5, P < 0.001) and had more diabetes (41.3% vs. 19.6%, P < 0.001) but male patients had more hypertension (46.8% vs. 28.1%, P = 0.002) and current smoker was more frequent in men (46.2% vs. 16.5%, P < 0.001). Among the patients above 65 years old, there was no sexual differences in the frequency of GST T1 null genotype between women and men, 46.3% (56/121) vs. 46.2% (73/158) ( P = 1.000) and the frequency of GST M1 null genotype also was not different, 49.6% (60/121) vs. 48.7% (77/158) (P = 0.904). Conclusion: The GST T1 null genotype was associated with increased risk of CAD in women, younger than 65 years old. It may be speculated that the increased oxidative stress from GST T1 mutation could be one of the possible pathogenesis of CAD in women, younger than 65 years with lower burden of conventional risk factors.
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