Niemiec Pawel, Nowak Tomasz, Iwanicki Tomasz, Krauze Jolanta, Gorczynska-Kosiorz Sylwia, Grzeszczak Wladyslaw, Ochalska-Tyka Anna, Zak Iwona
Department of Biochemistry and Medical Genetics, School of Health Sciences, Medical University of Silesia, Medykow Str 18, 40-752, Katowice, Poland,
Mol Biol Rep. 2014 May;41(5):3287-94. doi: 10.1007/s11033-014-3191-9. Epub 2014 Jan 31.
Reactive oxygen species (ROS) are involved in the pathogenesis of atherosclerosis and coronary artery disease (CAD). NADPH oxidases are the main source of ROS in the vasculature. p22phox is a critical component of vascular NADPH oxidases and is encoded by the CYBA (cytochrome b245 alpha) gene. The -930A>G CYBA polymorphism (rs9932581:A>G) modulates the activity of the CYBA promoter, and influences CYBA transcriptional activity. The aim of the present study was to analyze a possible association between the -930A>G polymorphism and CAD and to search for gene-traditional risk factors interactions. 480 subjects were studied: 240 patients with premature CAD, 240 age and sex matched blood donors. The -930A>G polymorphism was genotyped using the TaqMan® Pre-designed SNP Genotyping Assay (Applied Biosystems). The -930G allele carrier state was a risk factor for CAD (OR 2.03, 95% CI 1.21-3.44, P=0.007). A synergistic effect of the -930G allele with overweight/obesity (BMI≥25) and cigarette smoking was found. The estimated CAD risk for BMI≥25 and the -930G allele interaction was about 160% greater than that predicted by assuming additivity of the effects, and about 40% greater for interaction of cigarette smoking and the -930G allele. Overweight/obesity was a risk factor for CAD only in the -930G allele carriers (P<10(-10)) but not in the AA homozygotes (P=1.00). In conclusion the -930A>G CYBA polymorphism is associated with CAD in the Polish population. The -930G allele carriers are particularly at risk of consequences of obesity and tobacco smoke exposure.
活性氧（ROS）参与动脉粥样硬化和冠状动脉疾病（CAD）的发病机制。NADPH氧化酶是血管中ROS的主要来源。p22phox是血管NADPH氧化酶的关键成分，由CYBA（细胞色素b245α）基因编码。CYBA基因-930A>G多态性（rs9932581:A>G）调节CYBA启动子的活性，并影响CYBA转录活性。本研究的目的是分析-930A>G多态性与CAD之间的可能关联，并寻找基因与传统危险因素的相互作用。对480名受试者进行了研究：240例早发CAD患者，240名年龄和性别匹配的献血者。使用TaqMan®预设计SNP基因分型检测法（应用生物系统公司）对-930A>G多态性进行基因分型。-930G等位基因携带者状态是CAD的危险因素（比值比2.03，95%置信区间1.21-3.44，P=0.007）。发现-930G等位基因与超重/肥胖（BMI≥25）和吸烟存在协同效应。BMI≥25与-930G等位基因相互作用的估计CAD风险比假设效应相加所预测的风险高约160%，吸烟与-930G等位基因相互作用的风险高约40%。超重/肥胖仅在-930G等位基因携带者中是CAD的危险因素（P<10^(-10)），而在AA纯合子中不是（P=1.00）。总之，CYBA基因-930A>G多态性与波兰人群的CAD相关。-930G等位基因携带者尤其面临肥胖和接触烟草烟雾后果的风险。
