脓毒症基因多态性的研究新进展

蔡敏杰; 金莹莹; 林荣海; 徐颖鹤; 陈琪; 蒋永泼

doi:10.16766/j.cnki.issn.1674-4152.001838

脓毒症基因多态性的研究新进展

doi: 10.16766/j.cnki.issn.1674-4152.001838

1.
台州医院重症医学科，浙江台州 317000
2.
台州市中心医院重症医学科，浙江台州 318000

基金项目:

浙江省自然科学基金 LY20H150008

台州市科技计划项目 1902ky02

台州市科技计划项目 1801KY70

详细信息

通讯作者:
蒋永泼，E-mail：jyongpo8@163.com

中图分类号: R631 R446
计量
- 文章访问数: 146
- HTML全文浏览量: 106
- PDF下载量: 7
- 被引次数: 0
出版历程
- 收稿日期: 2020-03-21
- 网络出版日期: 2022-02-19

Recent developments of gene polymorphisms of sepsis

1.
Department of Critical Care Medicine, Taizhou Hospital of Zhejiang province, Wenzhou Medical University, Taizhou, Zhejiang 317000, China

摘要

摘要: 脓毒症(sepsis)是感染引起宿主反应失调导致的危及生命的器官功能障碍，是临床危重症患者死亡的主要原因之一。最新研究表示脓毒症发病率每年以1.5%~9.0%的速度持续增长，其病死率也居高不下。随着对脓毒症研究的不断深入，人们对脓毒症的认识也有不断提升，特别是在基因水平层面。基因多态性和脓毒症之间的研究不断更新，通过寻找基因与脓毒症发展过程中有关蛋白的表达、炎症因子水平及其易感性等之间的相关性，从而探索其在脓毒症早期诊断和预后判断中所扮演的重要角色。比如传统方式确认脓毒症感染源，复杂、费时，影响因素较多，而基因水平上的研究更加快速诊断，同时可发现新生物标志物，如髓样分化蛋白2(MD-2)、BTLA基因、内皮细胞蛋白C受体(EPCR)基因、16S rRNA基因等。而诊断是为了早期的治疗，迄今为止没有一项大数据报告在临床上实行真正基因水平上的治疗，更多的是通过对发病机制的研究，从而推断基因水平干预治疗方向。而较好的预后是持续治疗的前提，这对于大部分患者家庭而言是至关重要的一点。所以，治疗过程中能够提高预测精准性的水平尤为关键。这将是现今研究的热门方向，也是医学上渴望找到降低脓毒症死亡率的重点研究方向之一。本文对脓毒症基因多态性研究进展进行文献复习及综述。
- 脓毒症 /
- 基因多态性 /
- 诊断 /
- 预后
Abstract: Sepsis is a life-threatening organ dysfunction caused by the dysregulation of host response due to infection. This condition is one of the main causes of death in clinically critical patients. Recent research shows that the incidence of sepsis continues to increase at a rate of 1.5%-9.0% annually, and the mortality rate is also high. As research on sepsis has continuously progressed, our understanding of sepsis, especially at the genetic level, has improved. Research on the gene polymorphisms of sepsis is constantly updated by investigations on the correlation between genes and sepsis-related cell expression, protein expression, and inflammatory factors. Moreover, ongoing research focus on the susceptibility of these factors during the development of sepsis. Thus, the important role that these factors play must be determined to achieve early diagnosis of sepsis. Furthermore, these factors are crucial to the treatment and prognosis of sepsis at the genetic level. For example, the traditional method of identifying the source of infection is complicated, time-consuming, is influenced by numerous factors. Research on the genetic level of sepsis allows rapid diagnosis of sepsis and identification of new types of microorganisms, such as myeloid differentiation protein 2, BTLA gene polymorphism, endothelial cell protein C receptor gene and 16S rRNA gene. Early diagnosis of sepsis allows prompt treatment. Thus far, big data that can inform the clinical implementation of true gene-level treatment are lacking. Another research avenue is the study of the pathogenesis of sepsis, which can inform direction of treatment at the genetic level. The premise of continuous treatment is the good prognosis, which is crucial point to the patients' families. Therefore, the prediction accuracy during treatment of sepsis must be improved. Presently, this topic is the hotspot of research on sepsis to reduce mortality due to sepsis. The progress of research on the gene polymorphisms of sepsis is reviewed herein.
- Sepsis /
- Gene polymorphism /
- Diagnosis /
- Prognosis

HTML全文

参考文献(41)

[1]	王树云, 石齐芳, 杨光耀, 等. SF-1基因多态性与脓毒症肾上腺皮质功能不全的相关性研究[J]. 临床医学研究与实践, 2019, 4(34): 7-9, 12. https://www.cnki.com.cn/Article/CJFDTOTAL-YLYS201934003.htm
[2]	刘禹, 罗小敏, 道文欣, 等. Sting基因对脓毒症患者预后影响的研究[J]. 临床急诊杂志, 2020, 21(1): 48-54. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZLC202001007.htm
[3]	LU X, XUE L, SUN W B, et al. Identification of key pathogenic genes of sepsis based on the Gene Expression Omnibus database[J]. Mol Med Rep, 2018, 17(2): 3042-3054. http://www.onacademic.com/detail/journal_1000040143060310_00e3.html
[4]	吕其军, 史太阳, 周芳, 等. 16S rRNA基因检测在脓毒症早期诊断中的研究进展[J]. 中华医院感染学杂志, 2016, 26(10): 2395-2397. https://www.cnki.com.cn/Article/CJFDTOTAL-ZHYY201610077.htm
[5]	曹敬荣, 高世超, 陈典典, 等. 基于细菌16S rRNA基因扩增临床不常见病原菌的价值[J]. 中国感染控制杂志, 2016, 15(4): 222-226. doi: 10.3969/j.issn.1671-9638.2016.04.002
[6]	李满元, 赵劲松, 王学哲, 等. 16SrRNA基因检测在老年糖尿病烧伤脓毒症诊治中的价值[J]. 临床和实验医学杂志, 2019, 18(4): 398-401. doi: 10.3969/j.issn.1671-4695.2019.04.017
[7]	MIDAN D A, ABO EL FOTOH W M M, EL SHALAKANY A H. The potential role of incorporating real-time PCR and DNA sequencing for amplification and detection of 16S rRNA gene signatures in neonatal sepsis[J]. J Matern Fetal Neonatal Med, 2017, 30(12): 1476-1483. doi: 10.1080/14767058.2016.1219994
[8]	郑媛媛, 张良, 马国英, 等. 循环游离DNA联合16S rRNA基因检测在糖尿病烧伤脓毒症早期诊断中的作用[J]. 中华医院感染学杂志, 2019, 29(21): 3284-3287, 3292. https://www.cnki.com.cn/Article/CJFDTOTAL-ZHYY201921020.htm
[9]	秦桂秀, 黄瑞, 张莉, 等. 16S rRNA基因及多重聚合酶链式反应在新生儿败血症早期诊断中的应用研究[J]. 中国药物与临床, 2017, 17(11): 1566-1568. https://www.cnki.com.cn/Article/CJFDTOTAL-YWLC201711002.htm
[10]	丁红辉, 裴磊, 朱沅珍, 等. 巢式PCR方法在快速检测新生儿败血症病原菌中的应用[J]. 中国卫生检验杂志, 2016, 26(2): 204-205, 210. https://www.cnki.com.cn/Article/CJFDTOTAL-ZWJZ201602018.htm
[11]	GAUTAM P, LIGHT B, PURVIS T. Stability of two antifungal agents, fluconazole and miconazole, compounded in humco recura topical cream to determine beyond-use date[J]. Int J Pharm Compd, 2017, 21(2): 154-159
[12]	程少文, 陈晓松, 彭磊, 等. 创伤脓毒症易感基因多态性的研究进展[J]. 医学研究杂志, 2018, 47(1): 168-170, 174. https://www.cnki.com.cn/Article/CJFDTOTAL-YXYZ201801044.htm
[13]	陈影, 徐喜媛, 格日勒, 等. 脓毒症相关miRNA的基因芯片研究[J]. 临床肺科杂志, 2017, 22(10): 1802-1806. https://www.cnki.com.cn/Article/CJFDTOTAL-LCFK201710017.htm
[14]	刘绍灵, 彭国璇, 邓进. BTLA基因与炎症免疫调控研究进展[J]. 创伤外科杂志, 2017, 19(7): 555-557. doi: 10.3969/j.issn.1009-4237.2017.07.025
[15]	LIU Z L, HU J, XIAO X F, et al. The CD40 rs1883832 Polymorphism Affects Sepsis Susceptibility and sCD40L Levels[J]. Biomed Res Int, 2018.10.1155/2018/7497314 http://downloads.hindawi.com/journals/bmri/2018/7497314.pdf
[16]	梁燕冰, 覃月秋, 蒋玉洁, 等. EPCR基因rs2069940C/G、rs2069952C/T多态性与脓毒症易感性的相关性[J]. 广东医学, 2018, 39(7): 1000-1003. doi: 10.3969/j.issn.1001-9448.2018.07.011
[17]	梁燕冰, 覃月秋, 蒋玉洁, 等. 脓毒症患者内皮细胞蛋白C受体基因rs867186A/G位点多态性观察[J]. 山东医药, 2017, 57(19): 25-28. doi: 10.3969/j.issn.1002-266X.2017.19.007
[18]	SUN W, LI F S, ZHANG Y H, et al. Association of susceptibility to septic shock with platelet endothelial cell adhesion molecule-1 gene Leu125Val polymorphism and serum sPECAM-1 levels in sepsis patients[J]. Int J Clin Exp Med, 2015, 8(11): 20490-20498. http://www.ncbi.nlm.nih.gov/pubmed/26884965
[19]	LU H X, SUN J H, WEN D L, et al. LBP rs2232618 polymorphism contributes to risk of sepsis after trauma[J]. World J Emerg Surg, 2018, 13(1): 52. doi: 10.1186/s13017-018-0214-1
[20]	王海清, 左文, 陈睦虎, 等. 基因生物信息学的脓毒症潜在发病机制研究及生物标记物筛选[J]. 西南医科大学学报, 2018, 41(1): 27-31. doi: 10.3969/j.issn.2096-3351.2018.01.006
[21]	成正军, 何中林. PTEN在脓毒血症患者外周血单个核细胞的表达及其意义[J]. 中国普外基础与临床杂志, 2016, 23(10): 1243-1248. doi: 10.7507/1007-9424.20160319
[22]	ZHANG H, LU Y, SUN G, et al. The common promoter polymorphism rs11666254 downregulates FPR2/ALX expression and increases risk of sepsis in patients with severe trauma[J]. Crit Care, 2017, 21(1): 171. doi: 10.1186/s13054-017-1757-3
[23]	ACAR L, ATALAN N, KARAGEDIK E H, et al. Tumour necrosis factor-alpha and nuclear factor-kappa B gene variants in sepsis[J]. Balkan Med J, 2018, 35(1): 30-35. doi: 10.4274/balkanmedj.2017.0246
[24]	GEORGESCU A M, BANESCU C, AZAMFIREI R, et al. Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression[J]. BMC Infect Dis, 2020, 20(1): 221. doi: 10.1186/s12879-020-4910-6
[25]	CHEN Q X, YANG Y, HOU J C, et al. Increased gene copy number of DEFA1/DEFA3 worsens sepsis by inducing endothelial pyroptosis[J]. Proc Natl Acad Sci U S A, 2019, 116(8): 3161-3170. doi: 10.1073/pnas.1812947116
[26]	WANG M, YAN J J, HE X X, et al. Candidate genes and pathogenesis investigation for sepsis-related acute respiratory distress syndrome based on gene expression profile[J]. Biol Res, 2016, 49(1): 25. doi: 10.1186/s40659-016-0085-4
[27]	THIEBAUT P A, BESNIER M, GOMEZ E, et al. Role of protein tyrosine phosphatase 1B in cardiovascular diseases[J]. J Mol Cell Cardiol, 2016, 101: 50-57. doi: 10.1016/j.yjmcc.2016.09.002
[28]	钟俊, 杨国辉, 朱涛, 等. 血浆生长抑制特异性基因6浓度与重症脓毒症患者急性肺损伤的关系[J]. 广东医学, 2018, 39(17): 2619-2622. doi: 10.3969/j.issn.1001-9448.2018.17.015
[29]	YEH L C, HUANG P W, HSIEH K H, et al. Elevated plasma levels of Gas6 are associated with acute lung injury in patients with severe sepsis[J]. Tohoku J Exp Med, 2017, 243(3): 187-193. doi: 10.1620/tjem.243.187
[30]	孟建斌, 孙丽萍, 瓦永禄, 等. IL-23R的表达及基因多态性与脓毒症引起的急性肺损伤临床预后相关性[J]. 青海医学院学报, 2016, 37(3): 189-193. https://www.cnki.com.cn/Article/CJFDTOTAL-QHYX201603010.htm
[31]	WU Q, XU X M, REN J A, et al. Association between the -159C/T polymorphism in the promoter region of the CD14 gene and sepsis: a meta-analysis[J]. BMC Anesthesiology, 2017, 17(1): 11. doi: 10.1186/s12871-017-0303-9
[32]	赵昌明, 许磊, 郭东风, 等. C蛋白基因多态性对脓毒血症患者血小板功能的影响[J]. 现代生物医学进展, 2016, 16(20): 3905-3908. https://www.cnki.com.cn/Article/CJFDTOTAL-SWCX201620028.htm
[33]	胡豫, 王雅丹. 我如何治疗弥散性血管内凝血[Z]. 中华血液学杂志, 2017: 38(5), 371-374.
[34]	KATAYAMA S S, KOYAMA K, SHIMA J, et al. Thrombomodulin, plasminogen activator inhibitor-1 and protein c levels, and organ dysfunction in sepsis[J]. Critical Care Explorations, 2019, 1(5): e13. http://www.ncbi.nlm.nih.gov/pubmed/32166258
[35]	向桂霖, 张安强. 过氧化物酶体增殖物激活受体γ分子及基因多态性研究进展[J]. 解放军医学杂志, 2019, 44(9): 786-790. https://www.cnki.com.cn/Article/CJFDTOTAL-JFJY201909014.htm
[36]	CHEN F, WANG Y, ZHANG W Y, et al. A functional polymorphism-mediated disruption of EGR1/ADAM10 pathway confers the risk of sepsis progression[J]. mBio, 2019, 10(4): e01663-19. http://www.ncbi.nlm.nih.gov/pubmed/31387910
[37]	SHAO Y M, CHEN F, CHEN Y H, et al. Association between genetic polymorphisms in the autophagy-related 5 gene promoter and the risk of sepsis[J]. Sci Rep, 2017, 7(1): 9399. doi: 10.1038/s41598-017-09978-5
[38]	陈力, 刁波, 闫德祺, 等. HLA-DRB1基因多态性与儿童脓毒症易感性的相关性研究[J]. 华南国防医学杂志, 2019, 33(7): 468-472. https://www.cnki.com.cn/Article/CJFDTOTAL-HNGY201907007.htm
[39]	韩冬, 王雪松, 陈炜, 等. 脓毒症患者死亡危险因素及其与Toll样受体基因多态性相关分析[J]. 中华医院感染学杂志, 2019, 29(23): 3548-3552. https://www.cnki.com.cn/Article/CJFDTOTAL-ZHYY201923009.htm
[40]	TETTAMANTI C, HERVET T, GRABHERR S, et al. Elevation of NT-proBNP and cardiac troponins in sepsis-related deaths: a forensic perspective[J]. Int J Legal Med, 2016, 130(4): 1035-1043. doi: 10.1007/s00414-016-1360-1
[41]	ZHOU Y P, XIA Q, WANG X, et al. Endotoxin tolerant dendritic cells suppress inflammatory responses in splenocytes via interleukin-1 receptor associated kinase(IRAK)-M and programmed death-ligand 1(PDL-1)[J]. Medical Science Monitor, 2018, 24: 4798-4806. doi: 10.12659/MSM.908242