Protective Effects of FCGR2A Polymorphism in Invasive Pneumococcal Diseases

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 Fc gamma RIIa-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 Fc gamma RIIa-R/H131 genotypes (H/H, 25%; H/R, 53%; R/R, 22%) was comparable with that in the white control group. Comparison of the Fc gamma IIa-R/R131 and the Fc gamma RIIa-R/H131 + Fc gamma RIIa-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 Fc gamma RIIa-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 Fc gamma RIIa-R131 does not differ from that of other critically ill patients. However, the Fc gamma RIIa-R/R131 genotype was independently associated with increased survival, regardless of site of infection. CHEST 2012; 142(6):1474-1481