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Original Research: Chest Infections |

Protective Effects of FCGR2A Polymorphism in Invasive Pneumococcal DiseasesProtective Effects of FCGR2A Polymorphism

Adrien Bouglé, MD; Adeline Max, MD; Nicolas Mongardon, MD; David Grimaldi, MD; Frédéric Pène, MD, PhD; Christophe Rousseau, MSc; Jean-Daniel Chiche, MD, PhD; Jean-Pierre Bedos, MD; Eric Vicaut, MD, PhD; Jean-Paul Mira, MD, PhD
Author and Funding Information

From the Paris Descartes University (Drs Bouglé, Max, Mongardon, Grimaldi, Pène, Chiche, and Mira), Paris; Medical Intensive Care Unit (Drs Bouglé, Max, Mongardon, Grimaldi, Pène, Chiche, and Mira), Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris; Cochin Institute (Drs Grimaldi, Pène, Chiche, and Mira and Mr Rousseau), INSERM U1016/CNRS UMR8104; Paris Diderot University (Dr Vicaut), Paris; and Department of Biophysics (Dr Vicaut), Lariboisière University Hospital, Assistance Publique-Hôpitaux de Paris, Paris; and Intensive Care Unit (Dr Bedos), André Mignot Hospital, Le Chesnay, France.

Correspondence to: Jean-Paul Mira, MD, PhD, Medical Intensive Care Unit, Cochin University Hospital, 27 Rue du Faubourg Saint Jacques, 75014 Paris, France; e-mail: jean-paul.mira@cch.aphp.fr


Funding/Support: This study was supported by CARISMA (Cochin Association Research on Inflammation Sepsis and Molecular Advances).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(6):1474-1481. doi:10.1378/chest.11-2516
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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.

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