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Journal of ZheJiang University(Medical Science)  2016, Vol. 45 Issue (4): 410-415    DOI: 10.3785/j.issn.1008-9292.2016.07.12
    
Association of single nucleotide polymorphism in exon of transient receptor potential melastatin 2 gene with sepsis
FANG Minbo1,2, CHEN Qixing3, WU Shuijing1, FANG Xiangming1
1. Department of Anesthesiology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China;
2. Department of Anesthesiology, Ningbo Medical Treatment Center Lihuili Hospital, Ningbo 315000, China;
3. Clinical Research Center, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China
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Abstract  

Objective: To investigate the association between single nucleotide polymorphism (SNP) in the 11th exon of transient receptor potential melastatin 2 (TRPM2) gene with the susceptibility and outcome of sepsis. Methods: A total of 119 septic patients and 112 normal subjects were enrolled from the First Affiliated Hospital, Zhejiang University School of Medicine. Among 119 septic patients, 62 died (fatal group) and 57 survived (survival group) within 28 days of disease onset. The genotypes of these individuals were detected using TaqMan allelic discrimination assays, and its correlations with susceptibility and outcome of sepsis were analyzed. Results: There was no significant difference in genotype frequencies and allelic frequencies of TRPM2 SNP rs1556314 between septic patients and the controls (all P>0.05). And no significant difference in genotype frequencies and allelic frequencies of TRPM2 SNP rs1556314 was observed between the survivors and fatal cases of septic patients (all P>0.05). Conclusion: The TRPM2 SNP rs1556314 does not have significant association with sepsis, but this result need to be confirmed by large scale studies.



Key wordsSepsis      Transient receptor potential channels/physiology      Exons/genetics      Polymorphism,single nucleotide      Alleles      Case-control studies     
Received: 26 April 2016     
CLC:  R44  
  R515.3  
Cite this article:

FANG Minbo, CHEN Qixing, WU Shuijing, FANG Xiangming. Association of single nucleotide polymorphism in exon of transient receptor potential melastatin 2 gene with sepsis. Journal of ZheJiang University(Medical Science), 2016, 45(4): 410-415.

URL:

http://www.zjujournals.com/xueshu/med/10.3785/j.issn.1008-9292.2016.07.12     OR     http://www.zjujournals.com/xueshu/med/Y2016/V45/I4/410


瞬时受体电位通道M2外显子单核苷酸多态性rs1556314与脓毒症的相关性分析

目的:探讨瞬时受体电位通道M2(TRPM2)外显子单核苷酸多态性rs1556314与脓毒症发生、发展的相关性。方法:采用病例对照研究方法,将浙江大学医学院附属第一医院的119例脓毒症患者和112例对照者纳入本研究中。其中,脓毒症患者按照住院28 d转归不同分为存活组(57例)和死亡组(62例)。采用PCR-TaqMan探针技术检测TRPM2第11个外显子rs1556314基因型,分析其与脓毒症易感性及预后的关系。结果:TRPM2第11个外显子rs1556314基因型GG、GT、TT的分布频率脓毒症组与对照组之间差异无统计学意义(P>0.05),等位基因G、T的分布频率两组间差异亦无统计学意义(P>0.05)。在脓毒症死亡患者与存活患者中TRPM2第11个外显子rs1556314基因型GG、GT、TT和等位基因G、T分布频率差异均无统计学意义(均P>0.05)。结论:本研究结果提示TRPM2第11个外显子rs1556314的基因型和等位基因与脓毒症发生、发展无相关性,尚需大样本实验数据进一步证实。


关键词: 脓毒症,  瞬时受体电位通道/生理学,  外显子/遗传学,  多态性,单核苷酸,  等位基因,  病例对照研究 
[[1]]   SINGER M, DEUTSCHMAN C S, SEYMOUR C W, et al. The Third International Consensus Definitions for Sepsis and Shock (Sepsis-3)[J]. JAMA, 2016, 315(8):801-810.
[[2]]   ANGUS D C, VAN DER POLL T. Severe sepsis and septic shock[J]. N Engl J Med, 2013, 369(9):840-851.
[[3]]   ANGUS D C, LINDE-ZWIRBLE W T, LIDICKER J, et al. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care[J]. Crit Care Med, 2001, 29(7):1303-1310.
[[4]]   COHEN J. The immunopathogenesis of sepsis[J]. Nature, 2002, 420(6917):885-891.
[[5]]   JIANG L H, YANG W, ZOU J, et al. TRPM2 channel properties, functions and therapeutic potentials[J]. Expert Opin Ther Targets, 2010, 14(9): 973-988.
[[6]]   QIAN X, NUMATA T, ZHANG K, et al. Transient receptor potential melastatin 2 protects mice against polymicrobial sepsis by enhancing bacterial clearance[J]. Anesthesiology, 2014, 121(2):336-351.
[[7]]   LEVY M M, FINK M P, MARSHALL J C, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference[J]. Crit Care Med, 2003, 31(4):1250-1256.
[[8]]   GLAAB W E, SKOPEK T R. A novel assay for allelic discrimination that combines the fluorogenic 5' nuclease polymerase chain reaction (TaqMan) and mismatch amplification mutation assay[J]. Mutat Res, 1999, 430(1):1-12.
[[9]]   CHUNG L P, WATERER G W. Genetic predisposition to respiratory infection and sepsis[J]. Crit Rev Clin Lab Sci, 2011, 48(5-6):250-268.
[[10]]   NAMATH A, PATTERSON A J. Genetic polymorphisms in sepsis[J]. Crit Care Nurs Clin North Am, 2011, 23(1):181-202.
[[11]]   CHRISTAKI E, GIAMARELLOS-BOURBOULIS E J. The beginning of personalized medicine in sepsis: small steps to a bright future[J]. Clin Genet, 2014, 86(1):56-61.
[[12]]   WATANABE E, ZEHNBAUER B A, ODA S, et al. Tumor necrosis factor-308 polymorphism (rs1800629) is associated with mortality and ventilator duration in 1057 Caucasian patients[J]. Cytokine, 2012, 60(1):249-256.
[[13]]   TEUFFEL O, ETHIER M C, BEYENE J, et al. Association between tumor necrosis factor-alpha promoter-308 A/G polymorphism and susceptibility to sepsis and sepsis mortality: a systematic review and meta-analysis[J]. Crit Care Med, 2010, 38(1):276-282.
[[14]]   TISCHENDORF J J, YAGMUR E, SCHOLTEN D, et al. The interleukin-6(IL6)-174 G/C promoter genotype is associated with the presence of septic shock and the ex vivo secretion of IL6[J]. Int J Immunogenet, 2007, 34(6):413-418.
[[15]]   STANILOVA S A, MITEVA L D, KARAKOLEV Z T, et al. Interleukin10-1082 promoter polymorphism in association with cytokine production and sepsis susceptibility[J]. Intensive Care Med, 2006, 32(2):260-266.
[[16]]   CARREGARO F, CARTA A, CORDEIRO J A, et al. Polymorphisms IL10-819 and TLR-2 are potentially associated with sepsis in Brazilian patients[J]. Mem Inst Oswaldo Cruz, 2010, 105(5):649-656.
[[17]]   ARCAROLI J, SILVA E, MALONEY J P, et al. Variant IRAK-1 haplotype is associated with increased nuclear factor-kappaB activation and worse outcomes in sepsis[J]. Am J Respir Crit Care Med, 2006, 173(12):1335-1341.
[[18]]   THOMPSON C M, HOLDEN T D, RONA G, et al. Toll-like receptor 1 poly-morphisms and associated outcomes in sepsis after traumatic injury: a candidate gene association study[J]. Ann Surg, 2014, 259(1):179-185.
[[19]]   WURFEL M M, GORDON A C, HOLDEN T D, et al. Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis[J]. Am J Respir Crit Care Med, 2008, 178(7):710-720.
[[20]]   PINO-YANES M, CORRALES A, CASULA M, et al. Common variants of TLR1 associate with organ dysfunction and sustained pro-inflammatory responses during sepsis[J/OL]. PLoS One, 2010, 5(10):e13759.
[[21]]   LORENZ E, MIRA J P, FREES K L, et al. Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock[J]. Arch Intern Med, 2002, 162(9):1028-1032.
[[22]]   GIBOT S, CARIOU A, DROUET L, et al. Association between a genomic polymorphism within the CD14 locus and septic shock susceptibility and mortality[J]. Crit Care Med, 2002, 30(5):969-973.
[[23]]   LI L, NIE W, ZHOU H, et al. Association between plasminogen activator inhibitor-1-6754G/5G polymorphism and sepsis:a meta-analysis[J/OL]. PLoS One, 2013, 8(1):e54883.
[[24]]   CHEN Q X, WU S J, WANG H H, et al. Protein C-1641A/-1654C haplotype is associated with organ dysfunction and the fatal outcome of severe sepsis in Chinese Han population[J]. Hum Genet, 2008, 123(3):281-287.
[[25]]   CLAPHAM D E. TRP channels as celluar sensors[J]. Nature, 2003, 426(6966):517-524.
[[26]]   YAMAMOTO S, SHIMIZU S, KIYONAKA S, et al. TRPM2-mediated Ca2+ influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration[J]. Nature Med, 2008, 14(7):738-747.
[[27]]   WEHRHAHN J, KRAFT R, HARTENECK C, et al. Transient receptor potential melastatin 2 is required for lipopolysaccharide-induced cytokine production in human monocytes[J]. J Immunol, 2010, 184(5):2386-2393.
[[28]]   KNOWLES H, HEIZER J W, LI Y, et al. Transient receptor potential melastatin 2(TRPM2) ion channel is required for innate immunity against listeria monocytogenes[J]. Proc Natl Acad Sci U S A, 2011, 108(28):11578-11583.
[[29]]   KASHIO M, SOKABE T, SHINTAKU K, et al. Redox signal-mediated sensitization of transient receptor potential melastatin 2(TRPM2) to temperature affects macrophage functions[J]. Proc Natl Acad Sci U S A, 2012, 109(17):6745-6750.
[[30]]   DI A, GAO X P, QIAN F, et al. The redox-sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation[J]. Nat Immunol, 2012, 13(1):29-34.
[[31]]   KNOWLES H, LI Y, PERRAUD A L. TRPM2 ion channel, an oxidative stress and metabolic sensor regulating innate immunity and inflammation[J]. Immunol Res, 2013, 55(1-3):241-248.
[[32]]   MCQUILLIN A, BASS N J, KALSI G,et al. Fine mapping of a susceptibility locus for bipolar and genetically related unipolar affective disorders, to a region containing the C21ORF29 and TRPM2 genes on chromosome 21q22.3[J]. Mol Psychiatry, 2006, 11(2):134-142.
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