TAILOR-MADE MEDICINE AGAINST PATHOPHYSIOLOGICAL RESPONSE TO STRESS BASED ON THE GENOME ANALYSIS
Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants|
|Research Institution||CHIBA UNIVERSITY|
HIRASAWA Hiroyuki CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学研究院, 教授 (80114320)
ODA Shigeto CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 大学院・医学研究院, 助教授 (90204205)
SHIGA Hidetoshi CHIBA UNIVERSITY, UNIVERSITY HOSPITAL, ASSISSTANT PROFESSOR, 医学部附属病院, 講師 (20282478)
MATSUDA Kenichi CHIBA UNIVERSITY, UNIVERSITY HOSPITAL, ASSISSTANT PROFESSOR, 医学部附属病院, 講師 (60282480)
WATANABE Eizo CHIBA UNIVERSITY, UNIVERSITY HOSPITAL, ASSISSTANT, 医学部附属病院, 助手 (40375639)
上野 博一 千葉大学, 医学部附属病院, 助手 (70292688)
中西 加寿也 千葉大学, 医学部附属病院, 講師 (80272326)
|Project Period (FY)
2002 – 2004
Completed(Fiscal Year 2004)
|Budget Amount *help
¥8,800,000 (Direct Cost : ¥8,800,000)
Fiscal Year 2004 : ¥2,600,000 (Direct Cost : ¥2,600,000)
Fiscal Year 2003 : ¥2,600,000 (Direct Cost : ¥2,600,000)
Fiscal Year 2002 : ¥3,600,000 (Direct Cost : ¥3,600,000)
|Keywords||Cytokines / Polymorphism (Genetics) / SIRS / Multiple organ failure / Hypercytokinemia / Critical Care / Tailor-made medicine / hypercytokinemia|
Objective : To determine the allelic frequencies of interleukin(IL) -6, IL-1 and tumor necrosis factor-α(TNF)-related gene polymorphisms in critically ill patients with extremely high IL-6 blood level and to examine the genetic effects on their clinical courses.
Setting : A general intensive care unit(ICU).
Patients : One hundred and fifty consecutive critically ill patients recruited on admission to the ICU, regardless of diagnosis.
Measurements and Main Results : IL-6 blood levels were measured daily. Single nucleotide polymorphism at position -174 and -596 sites of the IL-6(IL6-174^*G/C and IL6-596^*G/A), -308 site of the TNF(TNF-308^*G/A) and -511 site of the IL-1β(IL1B-511^*C/T) were identified with real-time polymerase chain reaction(PCR) assay using specific fluorescence-labeled probe. IL-1 receptor antagonist intron 2 various number of tandem repeat polymorphism (IL1RN^*1-5) was identified after PCR with gel electrophoresis. Allelic frequencies of patients with IL-6 peak levels of
【greater than or equal】10,000 pg/mL (Group A) were compared with those of patients with IL-6 peak levels of <10,000 pg/mL (Group B). Neither IL6-174^*C nor IL6-596^* A were recognized in all the subjects, however Group A showed higher frequency of TNF-308^*A (p=.054), IL1-511^*T (p=.013) and non-IL1^*RN1(p=.008) allele compared with Group B. TNF-308^*A, IL1RN^*2 or IL1RN^*3 allele carriers of Group A showed sustained high IL-6 levels despite countermeasures against hypercytokinemia (ex.PMMA-CHDF), and their survival rate was lower than that of the non-carriers of those high-risk alleles (p=.025).
Conclusions : TNF-308^*A, IL1RN^*2 and IL1RN^*3 allele were associated with the prevalence of the extremely high IL-6 blood level in the critically ill, their uncontrollable blood IL-6 kinetics, and outcome. In TNF-308^*G/A, IL6-174^*G/C and IL6-596^*G/A, genotypic distributions in our Japanese populations were diverted from those in already reported Caucasian populations. Taking those into consideration, we should apply tailor-made medicine on the Japanese critically ill patients. Less
Research Products (15results)