title: Interleukin-10 rs2227307 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock.
abstract: Despite major improvements in its treatment and diagnosis, sepsis is still a leading cause of death and admittance to the intensive care unit (ICU). Failure to identify patients at high risk of developing septic shock contributes to an increase in the sepsis burden and rapid molecular tests are currently the most promising avenue to aid in patient risk determination and therapeutic anticipation. The primary goal of this study was to evaluate the genetic susceptibility that affects sepsis outcome in 72 sepsis patients admitted to the ICU. Seven polymorphisms were genotyped in key inflammatory response genes in sepsis, including tumour necrosis factor-α, interlelukin (IL)-1β, IL-10, IL-8, Toll-like receptor 4, CXCR1 and CXCR2. The primary finding showed that patients who were homozygous for the major A allele in IL-10 rs1800896 had almost five times higher chance to develop septic shock compared to heterozygotes. Similarly, selected clinical features and CXCR2 rs1126579 single nucleotide polymorphisms modulated septic shock susceptibility without affecting survival. These data support the hypothesis that molecular testing has clinical usefulness to improve sepsis prognostic models. Therefore, enrichment of the ICU portfolio by including these biomarkers will aid in the early identification of sepsis patients who may develop septic shock.
authors.affiliation: Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brasil.
authors.forename: Cristina Padre
authors.initials: CP
authors.lastname: Cardoso
authors.affiliation: Hospital Risoleta Tolentino Neves, Belo Horizonte, MG, Brasil.
authors.forename: Argenil José de Assis
authors.initials: AJ
authors.lastname: de Oliveira
authors.affiliation: Hospital Risoleta Tolentino Neves, Belo Horizonte, MG, Brasil.
authors.forename: Fernando Antônio
authors.initials: FA
authors.lastname: Botoni
authors.affiliation: Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: Isabela Cristina Porto
authors.initials: IC
authors.lastname: Rezende
authors.affiliation: Departamento de Farmacologia, Escola de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors.forename: Jose Carlos
authors.initials: JC
authors.lastname: Alves-Filho
authors.affiliation: Departamento de Farmacologia, Escola de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors.forename: Fernando de Queiroz
authors.initials: Fde Q
authors.lastname: Cunha
authors.affiliation: Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: Juliana de Assis Silva Gomes
authors.initials: Jde A
authors.lastname: Estanislau
authors.affiliation: Instituto Nacional de Ciência e Tecnologia de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: Luiz Alexandre Viana
authors.initials: LA
authors.lastname: Magno
authors.affiliation: Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso, Cuiabá, MT, Brasil.
authors.forename: Fabricio
authors.initials: F
authors.lastname: Rios-Santos
mesh_terms: D000368:Aged; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007362:Intensive Care Units; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011897:Random Allocation; D023063:Receptors, Interleukin-8B / Q000235:genetics*; D012772:Shock, Septic / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C508609:IL10 protein, human; D023063:Receptors, Interleukin-8B; D016753:Interleukin-10