中国呼吸与危重监护杂志

中国呼吸与危重监护杂志

p22phox C242T 基因多态性与阻塞性睡眠呼吸暂停并认知功能障碍的关系探讨

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目的 观察阻塞性睡眠呼吸暂停(OSA)患者–A930G、C242T 基因多态性与认知功能障碍的相关性,探讨由 CYBA 编码的 p22phox 等位基因在合并有认知功能障碍的 OSA 患者中的作用。 方法 选择 2014 年 9 月至 2016 年 11 月于呼吸睡眠科就诊的男性非吸烟 OSA 患者,其中认知功能障碍 OSA 患者 157 例,无认知功能障碍 OSA 患者 526 例。对患者进行认知功能评估、多导睡眠监测及遗传分析,ELISA 法测定还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NOX)活性和尿 8-羟基脱氧鸟苷(8-OH-dG)水平。 结果 –930G 等位基因携带者频率在两组受试者中差异无统计学意义(P>0.05)。无认知功能障碍的 OSA 受试者 TT/CT 基因型频率明显升高(P<0.05)。认知功能障碍的 OSA 受试者 NOX 活性较高(P<0.01),无等位基因 T 突变的受试者具有更高的 NOX 活性(P<0.05)。认知功能障碍的 OSA 受试者尿 8-OH-dG 水平较高(P<0.05),无等位基因 T 变异的受试者尿8-OH-dG 水平更高(P<0.05)。 结论 p22phox C242T 多态性可能参与了 OSA 合并认知功能障碍氧化应激的发生发展。

Objective To analyze a possible association of -A930G and C242T polymorphism with cognitive dysfunction in obstructive sleep apnea (OSA) patients, and assess potential interactions of CYBA alleles in OSA patients with cognitive dysfunction. Methods A total of 157 OSA patients with cognitive dysfunction were recruited as an experimental group, and 526 matched OSA patients without cognitive dysfunction as an control group. The neurocognitive assessment, polysomnography, genetic analyses, NADHP oxidase (NOX) activity, determination of urinary 8-OH-dG were completed in all subjects. Results Frequencies of the -930G allele carriers were not significantly different between two groups (P>0.05). Frequencies of the TT/CT genotypes were significantly higher in the OSA patients without cognitive dysfunction (P<0.05). NOX activity was assessed and found to be increased in the OSA patients with cognitive dysfunction (P<0.01). NOX activity was significantly higher in whom the allelic T variant was absent (P<0.05). The level of urinary 8-OH-dG was higher in the OSA patients with cognitive dysfunction (P<0.05). The level of urinary 8-OH-dG was significantly higher in whom the allelic T variant was absent (P<0.05). Conclusion The p22phox C242T polymorphism may be involved in the development of oxidative stress reaction in OSA patients with cognitive dysfunction.

关键词: 阻塞性睡眠呼吸暂停; 还原型烟酰胺腺嘌呤二核苷酸磷酸; 基因多态性; 认知功能障碍

Key words: Obstructive sleep apnea; Nicotinamide adenine dinucleotide phosphate; Gene polymorphism; Cognitive dysfunction

引用本文: 姜良征, 欧阳松云, 苏皎. p22phox C242T 基因多态性与阻塞性睡眠呼吸暂停并认知功能障碍的关系探讨. 中国呼吸与危重监护杂志, 2018, 17(4): 373-376. doi: 10.7507/1671-6205.201711036 复制

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1. Davies CR, Harrington JJ. Impact of obstructive sleep apnea on neurocognitive function and impact of continuous positive air pressure. Sleep Med Clin, 2016, 11(3): 287-298.
2. Batool-Anwar S, Kales SN, Patel SR, et al. Obstructive sleep apnea and psychomotor vigilance task performance. Nat Sci Sleep, 2014, 6: 65-71.
3. Olaithe M, Skinner TC, Hillman D, et al. Cognition and nocturnal disturbance in OSA: the importance of accounting for age and premorbid intelligence. Sleep Breath, 2015, 19(1): 221-230.
4. Sundaram SS, Halbower A, Pan Z, et al. Nocturnal hypoxia-induced oxidative stress promotes progression of pediatric non-alcoholic fatty liver disease. J Hepatol, 2016, 65(3): 560-569.
5. Parola M, Vajro P. Nocturnal hypoxia in obese-related obstructive sleep apnea as a putative trigger of oxidative stress in pediatric NAFLD progression. J Hepatol, 2016, 65(3): 470-472.
6. Tichanon P, Wilaiwan K, Sopida S, et al. Effect of continuous positive airway pressure on airway inflammation and oxidative stress in patients with obstructive sleep apnea. Can Respir J, 2016, 2016: 3107324.
7. Nair D, Dayyat EA, Zhang SX, et al. Intermittent hypoxia-induced cognitive deficits are mediated by NADPH oxidase activity in a urine model of sleep apnea. PLoS One, 2011, 6(5): e19847.
8. Zhan G, Serrano F, Fenik P, et al. NADPH oxidase mediates hypersomnolence and brain oxidative injury in a murine model of sleep apnea. Am J Respir Crit Care Med, 2005, 172(7): 921-929.
9. Djordjevic T, Pogrebniak A, BelAiba RS, et al. The expression of the NADPH oxidase subunit p22phox is regulated by a redox-sensitive pathway in endothelial cells. Free Radic Biol Med, 2005, 38(5): 616-630.
10. Liu HG, Liu K, Zhou YN, et al. Relationship between reduced nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox gene polymorphism and obstructive sleep apnea-hypopnea syndrome in the Chinese Han population. Chin Med J(Engl), 2009, 122(12): 1369-1374.
11. 刘辉国, 周燕宁, 刘馗, 等. 阻塞性睡眠呼吸暂停低通气综合征患者诱导痰中烟酰胺腺嘌呤二核苷酸磷酸氧化酶 p22phox 水平与病情的关系. 中华结核和呼吸杂志, 2010, 33(2): 118-122.
12. Gozal D, Khalyfa A, Capdevila OS, et al. Cognitive function in prepubertal children with obstructive sleep apnea: a modifying role for NADPH oxidase p22 subunit gene polymorphisms? Antioxid Redox Signal, 2012, 16(2): 171-177.
13. Moreno MU, San JG, Orbe J, et al. Preliminary characterisation of the promoter of the human p22(phox) gene: identification of a new polymorphism associated with hypertension. Febs Letters, 2003, 542(1-3): 27-31.
14. San JG, Moreno MU, Olivan S, et al. Functional effect of the p22phox -930A/G polymorphism on p22phox expression and NADPH oxidase activity in hypertension. Hypertension, 2004, 44(2): 163-169.
15. Moreno MU, San JG, Fortuno A, et al. The C242T CYBA polymorphism of NADPH oxidase is associated with essential hypertension. J Hypertens, 2006, 24(7): 1299-1306.
16. Wyche KE, Wang SS, Griendling KK, et al. C242T CYBA polymorphism of the NADPH oxidase is associated with reduced respiratory burst in human neutrophils. Hypertension, 2004, 43(6): 1246-1251.
17. Yu J, Li J, Huang X. The Beijing version of the Montreal cognitive assessment as a brief screening tool for mild cognitive impairment: a community-based study. BMC Psychiatry, 2012, 12(1): 156.
18. McLennan SN, Mathias JL, Brennan LC, et al. Validity of the Montreal cognitive assessment (MoCA) as a screening test for mild cognitive impairment (MCI) in a cardiovascular population. J Geriatr Psychiatry Neurol, 2011, 24(1): 33-38.
19. Lu D, Li P, Zhou Y, et al. Association between serum non-high-density lipoprotein cholesterol and cognitive impairment in patients with acute ischemic stroke. BMC Neurol, 2016, 16(1):154.
20. 康健, 王赞峰. 炎症、氧化应激与阻塞性睡眠呼吸暂停低通气综合征. 中华结核和呼吸杂志, 2006, 29(4): 226-227.
21. 刘颐轩, 宋桉, 王芸, 等. 氧化应激在肥胖及胰岛素抵抗中的作用研究进展. 解放军医药杂志, 2014, 26(1): 99-101.
22. 周骁, 杨会笃, 苏叶馨, 等. 氧化应激促进 AGT-REN 双转基因高血压小鼠心肌中电导钙激活钾离子通道表达. 中国病理生理杂志, 2016, 32(5):869-873.
23. Guzik TJ, West NE, Black E, et al. Functional effect of the C242T polymorphism in the NADPH oxidase p22phox gene on vascular superoxide production in atherosclerosis. Circulation, 2000, 102(15): 1744-1747.
24. Cahilly C, Ballantyne CM, Lim DS, et al. A variant of p22(phox), involved in generation of reactive oxygen species in the vessel wall, is associated with progression of coronary atherosclerosis. Circ Res, 2000, 86(4): 391-395.
25. Fang S, Wang L, Jia C. Association of p22phox gene C242T polymorphism with coronary artery disease: a meta-analysis. Thromb Res, 2010, 125(5): 197-201.
26. Xaplanteris P, Vlachopoulos C, Baou K, et al. The effect of p22(phox) -930A/G, A640G and C242T polymorphisms of NADPH oxidase on peripheral and central pressures in healthy, normotensive individuals. Hypertens Res, 2010, 33(8): 814-818.