Abstract
Severe sepsis and septic shock are the leading causes of death in intensive care units, and hence, in order to reduce mortality rates there is a great need for new discoveries. Genetic factors have been reported to alter clinical outcome of sepsis, and single nucleotide polymorphisms (SNPs) associations have been shown using cohorts of patients who had sepsis in various ethnicities. However, genetic studies for Japanese patients with sepsis are insufficiently powered for the development of personalized medicine. Therefore, we reviewed evidences reported in genetic polymorphisms studies that tested for genetic effect on clinical outcome of sepsis using cohorts with n >100 and reported after the year 2000 to develop personalized medicine for sepsis in Japan. Genetic variations in innate immunity, cytokine, chemokine, coagulation system, hormone, water channel and immunoglobulin have been interrogated. Of these genetic polymorphisms, TLR1, IL-1 receptor-associated kinases (IRAKs), NF-κB inducing kinase (NIK), nucleotide-binding oligomerization domain 2 (NOD2), IL-17A, protein C (PROC), β2-adrenergic receptor (ADRB2) and angiotensin II type 1 receptor-associated protein (AGTRAP) are significantly associated with an altered clinical outcome of sepsis in at least 2 separate cohorts. In addition, there is a large body of single cohort studies in which significant associations between SNPs and altered clinical outcome of sepsis have been reported as a hypothesis generating results, such as Mannose binding lectin and CXCL 2 polymorphisms with need for further validation. The genotypic frequencies of polymorphisms can vary across ethnicities, and the frequencies of functional SNPs that alter clinical outcome are no exception. In order to avoid population stratification effects due to differences in allele frequencies across different ethnicities, further genetic studies using Japanese patients are essential to achieve personalized medicine for these patients in need.
