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- 2016
炎症小体Nod样受体蛋白3及胱天蛋白酶募集域蛋白8基因多态性与急性冠脉综合征的相关性
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Abstract:
摘要：目的?? 探讨Nod样受体蛋白3(NLRP3)rs10754558位点C>G和胱天蛋白酶募集域蛋白8(CARD8)rs2043211位点A>T多态性与急性冠脉综合征(ACS)发病的关系。 方法?? 入选450例ACS患者和380例对照组人群，使用ABI Snapshot方法分析NLRP3 rs10754558位点和CARD8 rs2043211位点多态性；冠状动脉造影后以Gensini评分评价冠脉狭窄程度；Elisa测定血清白细胞介素-1β(IL-1β)浓度。结果 NLRP3 rs10754558位点对照组和ACS组基因型频率比较差异有统计学意义 (χ2=7.64，P=0.022)，NLRP3 rs10754558位点G等位基因与ACS发病相关(AOR=1.334，95% CI=1.085～1.642，P=0.006)。而CARD8 rs2043211位点两组间基因型频率比较差异无统计学意义(χ2=1.08，P=0.582)，且与ACS发病无明显关系(AOR=1.168，95% CI=0.942～1.449，P=0.156)。ACS患者NLRP3 rs10754558位点GG基因型Gensini评分高于CC基因型(74.07±2.13 vs. 42.91±1.80，P<0.001)；IL-1β质量浓度GG基因型显著高于CC基因型[(3.21±2.68)pg/mL vs. (1.37±1.36)pg/mL, P<0.001]。 结论 NLRP3 rs10754558位点C>G基因多态性与中国汉族人群ACS发病及冠状动脉狭窄程度有关；G等位基因是ACS发病的危险等位基因，其作用与IL-1β浓度升高有关。
ABSTRACT: Objective?? To investigate the potential association of the Nodlike receptor protein 3 (NLRP3) rs10754558 and caspase recruitment domain-containing protein 8 (CARD8) rs2043211 SNPs with the occurrence of acute coronary syndrome (ACS). Methods?? The NLRP3 rs10754558 and CARD8 rs2043211 SNPs were analyzed using the ABI PRISM-Snapshot multiplex method in 450 Chinese Han patients with ACS and 380 controls in the case-control study. Coronary angiography was performed to evaluate the severity of coronary atherosclerosis by Gensini score. The content of IL-1β in serum was determined by ELISA. Results? ?The difference in rs10754558 allele frequency between the control group and the ACS group was significant (χ2= 7.64, P=0.022). The NLRP3 rs10754558 G allele was significantly associated with the occurrence of ACS (AOR=1.334, 95% CI=1.085-1.642, P=0.006), while CARD8 rs2043211 polymorphism was not involved (χ2=1.08, P=0.582). Patients with GG genotype of NLRP3 rs10754558 had a higher Gensini score than those with CC genotype (74.07±2.13 vs. 42.91±1.80, P<0.001). There was no significant difference in Gensini score among ACS patients with different genotypes of CARD8 rs2043211. In the ACS group, the level of IL-1β in patients with GG genotype of NLRP3 rs10754558 was significantly higher than those patients with CC genotype (3.21±2.68 vs. 1.37±1.36pg/mL, P<0.001). Conclusion?? The NLRP3 rs10754558 polymorphism is involved in the occurrence of ACS and the severity of coronary atherosclerosis in the Chinese Han population. G allele is the risk allele of ACS. The role of G allele may be associated with elevated level of IL-1β
| [1] | GONG P, LUO SH, LI XL, et al. Relation of ABO blood groups to the severity of coronary atherosclerosis: an Gensini score assessment[J]. Atherosclerosis, 2014, 237(2):748-753. |
| [2] | SCHRODER K, ZHOU R, TSCHOPP J. The NLRP3 inflammasome: a sensor for metabolic danger?[J]. Science, 2010, 327(5963):296-300. |
| [3] | XIAO H, LU M, LIN TY, et al. Sterol regulatory element binding protein 2 activation of NLRP3 inflammasome in endothelium mediates hemodynamic-induced atherosclerosis susceptibility[J]. Circulation, 2013, 128(6):632-642. |
| [4] | WEN H, TING JP, O？？NEILL LA. A role for the NLRP3 inflammasome in metabolic diseases―did Warburg miss inflammation?[J]. Nat Immunol, 2012, 13(4):352-357. |
| [5] | TANGI TN, ELMABSOUT AA, BENGTSSON T, et al. Role of NLRP3 and CARD8 in the regulation of TNF-alpha induced IL-1beta release in vascular smooth muscle cells[J]. Int J Mol Med, 2012, 30(3):697-702. |
| [6] | SATOH M, TABUCHI T, ITOH T, et al. NLRP3 inflammasome activation in coronary artery disease: results from prospective and randomized study of treatment with atorvastatin or rosuvastatin[J]. Clin Sci (Lond), 2014, 126(3):233-241. |
| [7] | 刘俊田. 动脉粥样硬化发病的炎症机制的研究进展[J]. 西安交通大学学报(医学版), 2015 (2):141-152. |
| [8] | DUEWELL P, KONO H, RAYNER KJ, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals[J]. Nature, 2010, 464(7293):1357-1361. |
| [9] | LUO B, LI B, WANG W, et al. NLRP3 gene silencing ameliorates diabetic cardiomyopathy in a type 2 diabetes rat model[J]. PLoS One, 2014, 9(8):e104771. |
| [10] | ROBERTS RL, Van RIJ AM, PHILLIPS L？a, et al. Interaction of the inflammasome genes CARD8 and NLRP3 in abdominal aortic aneurysms[J]. Atherosclerosis, 2011, 218(1):123-126. |
| [11] | HITOMI Y, EBISAWA M, TOMIKAWA M, et al. Associations of functional NLRP3 polymorphisms with susceptibility to food-induced anaphylaxis and aspirin-induced asthma[J]. J Allergy Clin Immunol, 2009, 124(4):779-785. |
| [12] | KASTBOM A, KLINGBERG E, VERMA D, et al. Genetic variants in CARD8 but not in NLRP3 are associated with ankylosing spondylitis[J]. Scand J Rheumatol, 2013, 42(6):465-468. |
| [13] | LIU J, LIU YY, LIU J, et al. Association between CARD8 rs2043211 polymorphism and inflammatory bowel disease: a meta-analysis[J]. Immunol Invest, 2015, 44(3):253-264. |
| [14] | CREA F, LIUZZO G. Pathogenesis of acute coronary syndromes[J]. J Am Coll Cardiol, 2013, 61(1):1-11. |
| [15] | PARAMEL GV, FOLKERSEN L, STRAWBRIDGE RJ, et al. CARD8 gene encoding a protein of innate immunity is expressed in human atherosclerosis and associated with markers of inflammation[J]. Clin Sci (Lond), 2013, 125(8):401-407. |
| [16] | GARCIA-BERMUDEZ M, LOPEZ-MEJIAS R, GONZALEZ-JUANATEY C, et al. CARD8 rs2043211 (p.C10X) polymorphism is not associated with disease susceptibility or cardiovascular events in Spanish rheumatoid arthritis patients[J]. DNA Cell Biol, 2013, 32(1):28-33. |
