| Project/Area Number |
22591732
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Okayama University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MORIMATSU Hiroshi 岡山大学, 岡山大学病院, 講師 (30379797)
NAGASAKA Takeshi 岡山大学, 岡山大学病院, 助教 (30452569)
SATO Tetsufumi 独立行政法人国立がん研究センター, 麻酔科集中治療科, 科長 (40362975)
MIZOBUCHI Satoshi 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (70311800)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | ARDS / ステロイド / 一塩基変異 / TBX21 / 遺伝子 / SNP / 予後 / P/F ratio / ALI / T-BOX / T-BET |
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| Research Abstract |
ARDS is a life threatening condition with mortality rates of about 40-60%. We thought that corticosteroids are one of logical choice for treatment of ARDS. A transcriptional factor T-bet, responsible for the induction of T helper (Th)1 cells and the repression of Th2 cells from naive T lymphocytes, is encoded by the gene TBX21. Only one common nonsynonymous TBX21 SNP has been described to date, which codes for a replacement of histidine 33 with glutamine (H33Q). Tantisira KG et al reported that the nonsynonymous variation in TBX21 coding for replacement of H33Q is associated with significant improvement in the PC20 (a measure of airway responsiveness) of asthmatic children. Additionally, Tantisira KG et al alsoreported the TBX21 variant H33Q increases T helper 1 and decreases T helper 2 cytokine expression comparably with wild type H33H. Hence, the TBX21 variant H33Q will have a potential to improve airway responsiveness. Therefore, herein this study, we thought that H33Q in TBX21 will
… More
also be a predictor for improvement in ARDS with the use of corticosteroids. We developed a Restriction Fragment Length Polymorphism(RFLP) method to examine influence of H33Q of the TBX21 gene to the therapy with corticosteroids in ARDS patients. The status of common nonsynonymous TBX21 SNP was compared with clinical outcome and status of ARDS patients. TBX21 SNP analysis was done in32 cases. Among the 32 patients, 25 (78%) patients showed H33H, 6 (19%) patients showed H33Q, and one patient (3%) showed Q33Q phenotype in the TBX21 gene. In the H33Q/Q33Q group, ARDS patients with functional variant in the TBX21 gene have a possibility to show better outcomes when they treated with some kind of corticosteroids.In addition, we found a case with homozygous functional variant of Q33Q of the TBX21 gene. The case shows dramatic pharmacogenetic response to the therapy with corticosteroids. The PaO2/FiO2 ratio increased from 49 to 220 and pulmonary edema clearly improved after administration of corticosteroids. We found ARDS patients with functional variants in the TBX21 gene, especially Q33Q, have a possibility to show better outcomes when they treated with some kind of corticosteroids. Less
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