title: Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: a case-control study.
abstract: BACKGROUND
  Some patients have a greater response to viral infection than do others having a similar level of viral replication. Hypercytokinemia is the principal immunopathological mechanism that contributes to a severer clinical course in cases of influenza A/H1N1. The benefit produced, or damage caused, by these cytokines in severe disease is not known. The genes that code for these molecules are polymorphic and certain alleles have been associated with susceptibility to various diseases. The objective of the present study was to determine whether there was an association between polymorphisms of TNF, LTA, IL1B, IL6, IL8, and CCL1 and the infection and severity of the illness caused by the pandemic A/H1N1 in Mexico in 2009.
  
  
  METHODS
  Case-control study. The cases were patients confirmed with real time PCR with infection by the A/H1N1 pandemic virus. The controls were patients with infection like to influenza and non-familial healthy contacts of the patients with influenza. Medical history and outcome of the disease was registered. The DNA samples were genotyped for polymorphisms TNF rs361525, rs1800629, and rs1800750; LTA rs909253; IL1B rs16944; IL6 rs1818879; IL8 rs4073; and CCL1 rs2282691. Odds ratio (OR) and the 95% confidence interval (95% CI) were calculated. The logistic regression model was adjusted by age and severity of the illness in cases.
  
  
  RESULTS
  Infection with the pandemic A/H1N1 virus was associated with the following genotypes: TNF rs361525 AA, OR = 27.00; 95% CI = 3.07-1248.77); LTA rs909253 AG (OR = 4.33, 95% CI = 1.82-10.32); TNF rs1800750 AA (OR = 4.33, 95% CI = 1.48-12.64); additionally, LTA rs909253 AG showed a limited statistically significant association with mortality (p = 0.06, OR = 3.13). Carriers of the TNF rs1800629 GA genotype were associated with high levels of blood urea nitrogen (p = 0.05); those of the TNF rs1800750 AA genotype, with high levels of creatine phosphokinase (p=0.05). The IL1B rs16944 AA genotype was associated with an elevated number of leukocytes (p <0.001) and the IL8 rs4073 AA genotype, with a higher value for PaO2 mm Hg.
  
  
  CONCLUSIONS
  The polymorphisms of genes involved in the inflammatory process contributed to the severity of the clinical behavior of infection by the pandemic influenza A/H1N1 virus.
authors.affiliation: Coordinación de Investigación en Salud, Instituto Mexicano del Seguro Social (IMSS), Torre Academia Nacional de Medicina 4to piso, Av, Cuauhtémoc 330, 06720 México, DF, México.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Morales-García
authors.forename: Ramcés
authors.initials: R
authors.lastname: Falfán-Valencia
authors.forename: Román Alejandro
authors.initials: RA
authors.lastname: García-Ramírez
authors.forename: Ángel
authors.initials: Á
authors.lastname: Camarena
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ramirez-Venegas
authors.forename: Manuel
authors.initials: M
authors.lastname: Castillejos-López
authors.forename: Martha
authors.initials: M
authors.lastname: Pérez-Rodríguez
authors.forename: César
authors.initials: C
authors.lastname: González-Bonilla
authors.forename: Concepción
authors.initials: C
authors.lastname: Grajales-Muñíz
authors.forename: Víctor
authors.initials: V
authors.lastname: Borja-Aburto
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Mejía-Aranguré
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000302:isolation & purification* / Q000472:pathogenicity; D007251:Influenza, Human / Q000235:genetics* / Q000276:immunology / Q000473:pathology* / Q000821:virology; D008297:Male; D008800:Mexico; D008875:Middle Aged; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D016207:Cytokines