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 (IPD). However, previous reports needed confirmation in a large well-defined population. METHODS:Prospective genetic association study in a 24-bed medical ICU of a tertiary teaching hospital over 7 years. DNA from all Caucasian patients with IPD (pneumonia and/or meningitis) was genotyped for the FcγRIIa-R/H131 polymorphism. RESULTS:243 patients with proven IPD were enrolled, 202 (82%) with pneumonia and 55 (22%) with meningitis. Mean age was 61 yo, mean SAPS2 was 50.4, half of the patients had bacteremia, 84% of the cohort was mechanically ventilated and the hospital mortality rate was 31%. In the IPD group, distribution of the FcγRIIa-R/H131 genotypes (H/H: 25%; H/R: 53%; RR: 22%) was comparable to distribution in the Caucasian control group. Comparison of the FcγRIIa-R/R131 and the (FcγRIIa-R/H131 + FcγRIIa-H/H131) groups did not demonstrate any difference for age, SAPS2, origin of sepsis and other co-morbid conditions. However, the variant FcγRIIa-R/R131 genotype was independently associated with decreased hospital mortality (OR = 0,251, IC [0,098-0,645]; p = 0,004). CONCLUSION:In a well-defined population of IPD patients, frequency of the variant FcγRIIa-R131 does not differ from other critically ill patients. However, the FcγRIIa-R/R131 genotype was independently associated with increased survival regardless of site of infection.