title: Genetic variants of the MBL2 gene are associated with mortality in pneumococcal sepsis.
abstract: Studies evaluating associations between polymorphisms of innate immunity genes and prognosis of infectious diseases have yielded conflicting results. Our aim was to assess the impact on mortality of different genotypic variants of the innate immunity in patients with pneumococcal sepsis. All adults admitted to the hospital with diagnosis of sepsis caused by Streptococcus pneumoniae were enrolled and single-nucleotide polymorphisms (SNP) in mannose-binding lectin 2 (MBL2), toll-like receptor (TLR) 2, TLR4, and Fcγ receptor IIa genes were genotyped. Underlying diseases, severity of illness, and antibiotic management were also recorded. We included 117 patients: 98 pneumonias (83.6%), 17 meningitis (14.5%), and 2 patients (1.9%) with primary pneumococcal bacteremia. Allelic variants of the MBL2 gene (individuals heterozygous or homozygous for one of the 3 allelic variants B, C, and D: AO/OO) were present in 37 patients (32%), T399I polymorphism in TLR4 in 19 (16.2%), TLR4 D299G/T399I in 11 (9.4%), TLR2 R753Q in 3 (2.5%), and FcγRIIa-R/R131 in 26 patients (23%). Factors associated independently with in-hospital mortality were SNP MBL2 AO/OO (adjusted hazard ratios [aHR] 3.2, 95% confidence interval [CI] 1.01-9.8) and septic shock (aHR 15.3, 95% CI 3.5-36.5), whereas first adequate antibiotic dose ≤ 4 h was a protective factor (aHR 0.2, 95% CI 0.06-0.8). SNP MBL2 AO/OO (aHR 2.2, 95% CI 1.1-8.1) remained as a variable independently associated with 90-day mortality. In conclusion, variant alleles in the MBL2 gene are independently associated with in-hospital and medium-term mortalities in patients admitted to the hospital with pneumococcal sepsis.
authors.affiliation: Critical Care and Emergency Department, Hospital Universitario Virgen del Rocío, Seville, Spain. jgarnachom@telefonica.net
authors.forename: José
authors.initials: J
authors.lastname: Garnacho-Montero
authors.forename: Emilio
authors.initials: E
authors.lastname: García-Cabrera
authors.forename: Rocio
authors.initials: R
authors.lastname: Jiménez-Álvarez
authors.forename: Ana
authors.initials: A
authors.lastname: Díaz-Martín
authors.forename: Jaume
authors.initials: J
authors.lastname: Revuelto-Rey
authors.forename: Javier
authors.initials: J
authors.lastname: Aznar-Martín
authors.forename: Carmen
authors.initials: C
authors.lastname: Garnacho-Montero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011008:Pneumococcal Infections / Q000235:genetics* / Q000401:mortality*; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000235:genetics; D018805:Sepsis / Q000235:genetics* / Q000401:mortality*; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D017452:Receptors, IgG; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4