Tailor-made medicine based on genetic polymorphism analyses in relation to biological and immunological responses

本研究旨在建立基于日本人群遗传多态性分析的量身定制药物。为了确定遗传对严重脓毒症病理生理的影响，我们研究了IL-1RA第2内含子可变数目串联重复序列（VNTR）多态性是否影响严重脓毒症的易感性和预后。此外，我们还评估了VNTR与体外细胞因子表达之间的关系。261名入住ICU（重症监护病房）的患者被纳入发现队列，793名入住5个不同研究所的ICU患者被纳入验证队列。IL1RA RN^*2被认为是较少的IL-1ra产生者，在日本人群中，通过降低对某些炎症细胞因子产生的调节潜力，与严重败血症的不良结局相关。

This study aims to establish the tailor-made medicine based on genetic polymorphism analysis in Japanese population. To determine the genetic effects on pathophysiology of severe sepsis, we investigated whether IL-1RA 2nd intron variable number of tandem repeat (VNTR) polymorphism bears influences on the susceptibility to and the outcome of severe sepsis. And, we also evaluated association between the VNTR and ex vivo expression of cytokines. Two hundred and sixty one patients who had admitted to an ICU (intensive care unit) were enrolled into a discovery cohort and 793 ICU patients admitted to the 5 different institutes were enrolled into a validation cohort. The IL1RA RN^*2, which was suggested to be a less IL-1ra producer, was associated with adverse outcome of severe sepsis via lower regulatory potential against some inflammatory cytokine production in Japanese population.