title: Protective effects of FCGR2A polymorphism in invasive pneumococcal diseases.
abstract: BACKGROUND
  Streptococcus pneumoniae is a major cause of pneumonia and meningitis. Several genetic polymorphisms have been described to explain differences in susceptibility and severity of encapsulated pathogen-related diseases. Among them, a functional FCGR2A polymorphism leading to amino acid change of histidine (H) to arginine (R) at position 131 appears to be a major candidate in adult invasive pneumococcal diseases (IPDs). However, previous reports need confirmation in a large, well-defined population.
  
  
  METHODS
  This prospective genetic association study was carried out in a 24-bed medical ICU of a tertiary teaching hospital over 7 years. DNA from all white patients with IPD (pneumonia or meningitis) was genotyped for the FcγRIIa-R/H131 polymorphism.
  
  
  RESULTS
  A total of 243 patients with IPD were enrolled; 202 (82%) had pneumonia, and 55 (22%) had meningitis. Mean age was 61 years, and mean Simplified Acute Physiology Score II was 50.4. One-half of the patients had bacteremia, and 84% of the cohort received mechanical ventilation. The hospital mortality rate was 31%. In the IPD group, the distribution of the FcγRIIa-R/H131 genotypes (H/H, 25%; H/R, 53%; R/R, 22%) was comparable with that in the white control group. Comparison of the FcγRIIa-R/R131 and the FcγRIIa-R/H131 + FcγRIIa-H/H131 groups did not demonstrate any difference for age, Simplified Acute Physiology Score II, origin of sepsis, and other comorbid conditions. However, the variant FcγRIIa-R/R131 genotype was independently associated with decreased hospital mortality (OR, 0.251; 95% CI, 0.098-0.645; P = .004).
  
  
  CONCLUSIONS
  In a well-defined population of patients with IPD, the frequency of the variant FcγRIIa-R131 does not differ from that of other critically ill patients. However, the FcγRIIa-R/R131 genotype was independently associated with increased survival, regardless of site of infection.
authors.affiliation: Paris Descartes University, Paris; Medical Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris.
authors.forename: Adrien
authors.initials: A
authors.lastname: Bouglé
authors.affiliation: Paris Descartes University, Paris; Medical Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris.
authors.forename: Adeline
authors.initials: A
authors.lastname: Max
authors.affiliation: Paris Descartes University, Paris; Medical Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mongardon
authors.affiliation: Paris Descartes University, Paris; Medical Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris; Cochin Institute, INSERM U1016/CNRS UMR8104, Paris.
authors.forename: David
authors.initials: D
authors.lastname: Grimaldi
authors.affiliation: Paris Descartes University, Paris; Medical Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris; Cochin Institute, INSERM U1016/CNRS UMR8104, Paris.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pène
authors.affiliation: Cochin Institute, INSERM U1016/CNRS UMR8104, Paris.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rousseau
authors.affiliation: Paris Descartes University, Paris; Medical Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris; Cochin Institute, INSERM U1016/CNRS UMR8104, Paris.
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Chiche
authors.affiliation: Intensive Care Unit, André Mignot Hospital, Le Chesnay, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bedos
authors.affiliation: Paris Diderot University, Paris; Department of Biophysics, Lariboisière University Hospital, Assistance Publique-Hôpitaux de Paris, Paris.
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.affiliation: Paris Descartes University, Paris; Medical Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris; Cochin Institute, INSERM U1016/CNRS UMR8104, Paris. Electronic address: jean-paul.mira@cch.aphp.fr.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Mira
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D017452:Receptors, IgG / Q000235:genetics*; D012121:Respiration, Artificial; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate
chemical_list: C445323:FCGR2A protein, human; D017452:Receptors, IgG