Variants in LTA, TNF, IL1B and IL10 genes associated with the clinical course of sepsis.
The aim of this study was to explore the association between some SNPs of the TNF, LTA, IL1B and IL10 genes with cytokine concentrations and clinical course in Colombian septic patients. We conducted a cross-sectional study to genotype 415 septic patients and 205 patients without sepsis for the SNPs -308(G/A) rs1800629 of TNF; +252 (G/A) rs909253 of LTA; -511(A/G) rs16944 and +3953(C/T) rs1143634 of IL1B; and -1082(A/G) rs1800896, -819(C/T) rs1800871 and -592(C/A) rs1800872 of IL10. The association of theses SNPs with the following parameters was evaluated: (1) the presence of sepsis; (2) severity and clinical outcomes; (3) APACHE II and SOFA scores; and (4) procalcitonin, C-reactive protein, tumor necrosis factor, lymphotoxin alpha, interleukin 1 beta and interleukin 10 plasma concentrations. We found an association between the SNP LTA +252 with the development of sepsis [OR 1.29 (1.00-1.68)]; the SNP IL10 -1082 with sepsis severity [OR 0.53 (0.29-0.97)]; the TNF -308 with mortality [OR 0.33 (0.12-0.95)]; and the IL10 -592 and IL10 -1082 with admission to the intensive care unit (ICU) [OR 3.36 (1.57-7.18)] and [OR 0.18 (0.04-0.86)], respectively. None of the SNPs were associated with cytokine levels, procalcitonin and C-reactive protein serum concentrations, nor with APACHE II and SOFA scores. Our results suggest that these genetic variants play an important role in the development of sepsis and its clinical course.
Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
Carolina
0000-0002-4847-3021
C
Montoya-Ruiz
Grupo Académico de Epidemiologia Clínica, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.|Departamento de Medicina Interna, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.|Unidad de Investigaciones, Hospital Pablo Tobón Uribe Medellín, Calle 78B No. 69-240, Medellín, Colombia.
Fabián A
FA
Jaimes
Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
Maria T
MT
Rugeles
Escuela de Microbiología, Grupo Inmunodeficiencias Primarias-Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
Juan Álvaro
JÁ
López
Grupo Genética Molecular, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
Gabriel
G
Bedoya
Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia. paula.velilla@udea.edu.co.|School of Medicine, University of Antioquia, Carrera 53 No. 61-30 Lab. 532, Sede de Investigación Universitaria - SIU, Medellín, Colombia. paula.velilla@udea.edu.co.
Paula A
PA
Velilla
D002097:C-Reactive Protein / Q000378:metabolism; D002116:Calcitonin / Q000097:blood; D003105:Colombia; D003422:Critical Care; D003430:Cross-Sectional Studies; D018450:Disease Progression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics*; D008233:Lymphotoxin-alpha / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018805:Sepsis / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
D053583:Interleukin-1beta; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002116:Calcitonin; D002097:C-Reactive Protein
Colombian population; Cross-sectional study; Cytokines; Infection; SIRS; SNP; Sepsis