长链非编码RNA及与环境因素交互作用对冠心病患病的影响
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摘要
目的探讨外周血白细胞长链非编码RNA(long noncoding RNA,lncRNA)和环境因素在冠心病患病中的作用。方法采用病例-对照研究的方法,利用分层随机抽样的方法于2015年3月至2017年12月在福州市某医院收集冠心病病例和健康对照,进行问卷调查、健康体检和实验室检测。采用实时荧光定量PCR方法检测lncRNA(NR_027032、NR_047116和NR_104181)在病例组和对照组中的表达情况。采用多因素Logistic回归模型、叉生分析等分析环境因素和lncRNA在冠心病患病中的联合及交互作用。结果病例组外周血白细胞中NR_027032、NR_047116和NR_104181的表达水平低于对照组(P<0.05);多因素Logistic回归分析结果显示,NR_027032、NR_047116和NR_104181低表达可增加冠心病患病风险。叉生分析结果显示,超重与NR_047116低表达同时存在时冠心病患病风险是非超重且无NR_047116低表达的19.053倍(95%CI 5.159～70.361)。超重与NR_047116低表达基于相加模型的交互作用有统计学意义(U=1.999,P=0.046),各评价指标:S=0.598,AP=10.070,RERI=0.629。结论冠心病是环境因素和遗传因素共同作用的结果,NR_047116低表达与超重的联合作用及相加交互作用可增加冠心病的患病风险。
OBJECTIVE To investigate the role of leukocyte long noncoding RNA(lncRNA) and environmental factors on coronary heart disease(CHD).METHODS A case-control study was conducted in a hospital in Fuzhou City by using stratified random sampling method during March 2015 and December 2017. The related surveys included questionnaire investigation, physical examination and laboratory detection. And real-time fluorescence quantitative PCR was used to detect the expression of lncRNA(NR_027032, NR_047116 and NR_104181) in case group and control group. Multivariate Logistic regression models and crossover analysis were used to analyze the interaction and association of environmental factors and lncRNA on CHD. RESULTS Wilcoxon rank sum test indicated that: The expression levels of NR_027032, NR_047116 and NR_104181 in CHD were lower than those in control group, the difference was statistically significant(P<0.05). Multivariate Logistic regression analysis showed that the low expression of NR_027032, NR_047116 and NR_104181 may increase the risk of CHD. Crossover analysis showed that the risk of CHD was 19.053 times(95% CI 5.159-70.361) in the presence of overweight and low expression of NR_047116 than that in the normal condition. And the additive model between the two groups was statistically significant(U=1.999, P=0.046). The evaluation indexes were S=0.598, AP=10.070 and RERI=0.629. CONCLUSION CHD is the result of environmental factors and genetic factors. The association and additive effect of NR_047116 low expression and overweight may increase the risk of CHD.
OBJECTIVE To investigate the role of leukocyte long noncoding RNA(lncRNA) and environmental factors on coronary heart disease(CHD).METHODS A case-control study was conducted in a hospital in Fuzhou City by using stratified random sampling method during March 2015 and December 2017. The related surveys included questionnaire investigation, physical examination and laboratory detection. And real-time fluorescence quantitative PCR was used to detect the expression of lncRNA(NR_027032, NR_047116 and NR_104181) in case group and control group. Multivariate Logistic regression models and crossover analysis were used to analyze the interaction and association of environmental factors and lncRNA on CHD. RESULTS Wilcoxon rank sum test indicated that: The expression levels of NR_027032, NR_047116 and NR_104181 in CHD were lower than those in control group, the difference was statistically significant(P<0.05). Multivariate Logistic regression analysis showed that the low expression of NR_027032, NR_047116 and NR_104181 may increase the risk of CHD. Crossover analysis showed that the risk of CHD was 19.053 times(95% CI 5.159-70.361) in the presence of overweight and low expression of NR_047116 than that in the normal condition. And the additive model between the two groups was statistically significant(U=1.999, P=0.046). The evaluation indexes were S=0.598, AP=10.070 and RERI=0.629. CONCLUSION CHD is the result of environmental factors and genetic factors. The association and additive effect of NR_047116 low expression and overweight may increase the risk of CHD.
引文
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[2] MACK M,GOPAL A.Epidemiology,traditional and novel risk factors in coronary artery disease[J].Cardiol Clin,2014,32(3):323-332.
[3] YIN Q,WU A,LIU M.Plasma long non-coding RNA (lncRNA) GAS5 is a new biomarker for coronary artery disease[J].Med Sci Monit,2017,23:6042-6048.
[4] ZHU Y,YANG T,DUAN J,et al.MALAT1/miR-15b-5p/MAPK1 mediates endothelial progenitor cells autophagy and affects coronary atherosclerotic heart disease via mTOR signaling pathway[J].Aging,2019,11(4):1089-1109.
[5] HU Y W,GUO F X,XU Y J,et al.Long noncoding RNA NEXN-AS1 mitigates atherosclerosis by regulating the actin-binding protein NEXN[J].J Clin Invest,2019,129(3):1115-1128.
[6] TSE L A,LIN X,LI W,et al.Smoking cessation sharply reduced lung cancer mortality in a historical cohort of 3185 Chinese silicotic workers from 1981 to 2014[J].Br J Cancer,2018,119(12):1557-1562.
[7] SITI HAJAR M H,ZULKEFLI S,JUWITA S,et al.Metabolic,inflammatory,and oxidative stress markers in women exposed to secondhand smoke[J].Peer J,2018,6:e5758.
[8] LIANG J,WU X,SUN S,et al.Circular RNA expression profile analysis of severe acne by RNA-Seq and bioinformatics[J].J Eur Acad Dermatol Venereol,2018,32(11):1986-1992.
[9] 杜永成,李黎明,文乾灵,等.冠心病发病危险因素研究分析[J].内科,2016,11(1):29-31.
[10] LIN D C,LIN J B,CHEN Z,et al.Independent and combined effects of environmental factors and miR-126,miR-143,and miR-145 on the risk of coronary heart disease[J].J Geriatr Cardiol,2017,14(11):688-695.
[11] BLUMENTHAL J A,FEGER B J,SMITH P J,et al.Treatment of anxiety in patients with coronary heart disease:rationale and design of the UN derstanding the benefits of exercise and escitalopram in anxious patients with coronary heart disease (UNWIND) randomized clinical trial[J].Am Heart J,2016,176:53-62.
[12] FRITZ J,STROHMAIER S,NAGEL G,et al.A strong interaction between age and overweight/obesity on the risk of coronary heart disease in the context of metabolic mediation[J].Epidemiology,2016,27(3):e13.
[13] TARLETON H P,SMITH L V,ZHANG Z F,et al.Utility of anthropometric measures in a multiethnic population:their association with prevalent diabetes,hypertension and other chronic disease comorbidities[J].J Comm Health,2014,39(3):471-479.
[14] LI Z,BAI Y,GUO X,et al.Alcohol consumption and cardiovascular diseases in rural China[J].Int J Cardiol,2016,215:257-262.
[15] SONG R J,NGUYEN X M T,QUADEN R,et al.Alcohol consumption and risk of coronary artery disease (from the million veteran program)[J].Am J Cardiol,2018,121(10):1162-1168.
[16] FRANKLIN B A,DURSTINE J L,ROBERTS C K,et al.Impact of diet and exercise on lipid management in the modern era[J].Best Pract Res Clin Endocrinol Metab,2014,28(3):405-421.
[17] PETRONIS A.Epigenetics and twins:three variations on the theme[J].Trends Genet,2006,22(7):347-350.
[18] SUGAWARA H,IWAMOTO K,BUNDO M,et al.Hypermethylation of serotonin transporter gene in bipolar disorder detected by epigenome analysis of discordant monozygotic twins[J].Transl Psychia,2011,1:e24.
[19] KUIAN L,AGUIRRE A,SANCHOMARTINEZ I,et al.Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development[J].Circulation,2015,131(14):1278-1290.
[20] ANDREA B,BRUCE U,MARY S,et al.DNA hypomethylation,ambient particulate matter,and increased blood pressure:findings from controlled human exposure experiments[J].J Am Heart Assoc,2013,2(3):e000212.
[21] LICCHESI J D,WESTRA W H,HOOKER C M,et al.Promoter hypermethylation of hallmark cancer genes in atypical adenomatous hyperplasia of the lung[J].Clin Cancer Res,2008,14(9):2570-2578.
[22] BERTOZZI D,IURLARO R,SORDET O,et al.Characterization of novel antisense HIF-1alpha transcripts in human cancers[J].Cell Cycle,2011,10(18):3189-3197.
[23] YANG X J,OGRYZKO V V,NISHIKAWA J,et al.A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A[J].Nature,1996,382(6589):319-324.
[24] PARRA M,HERRERA D,CALVO-CALLE J M,et al.Circulating human rotavirus specific CD4 T cells identified with a class II tetramer express the intestinal homing receptors alpha 4 beta 7 and CCR9[J].Virology,2014,452-453:191-201.
[25] GUZIK T J,HOCH N E,BROWN K A,et al.Role of the T cell in the genesis of angiotensin II-induced hypertension and vascular dysfunction[J].J Exp Med,2007,204(10):2449-2460.
[26] SCHINZARI F,TESAURO M,CARDILLO C.Endothelial and perivascular adipose tissue abnormalities in obesity-related vascular dysfunction:novel targets for treatment[J].J Cardiovasc Pharmacol,2017,69(6):360-368.