Polymorphism ’protective in pneumococcal disease’

By Ingrid Grasmo

Patients with invasive pneumococcal disease (IPD) who have the FcyRIIa-R/R131 polymorphism may have better survival outcomes than those without the genotype, suggest study findings.

Streptococcus pneumoniae is an important cause of pneumonia and meningitis, but individuals show great differences in the susceptibility and severity of encapsulated pathogen-related diseases.

Previous studies suggest that a functional FCGR2A gene receptor polymorphism leading to amino acid change of histidine (H) to arginine (R) at position 131 appear to be a major candidate in adult IPD. The results from this study confirm these reports in a large and well-defined patient population.

"Carrying the FcyRIIa-R/R131 genotype is protective during IPD," say Jean‑Paul Mira (Cochin University Hospital, Paris, France) and co-authors.

Over a 7-year period, the researchers compared the frequency of FcyRIIa-R/H131 genotypes in a sample of 243 patients with proven IPD (82% with pneumonia and 22% with meningitis) with that in 2789 noninfected critically ill patients.

Half of the IPD patients were diagnosed with bacteremia and the average Simplified Acute Physiologic Score (SAPS) II was 50.4. Intensive care unit mortality rate was 25%, with an in-hospital mortality rate of 31%.

FCGR2A genotype distributions were comparable among IPD and control patients, at 25% and 26% for FcyRIIa-H/H131, 53% and 49% for FcyRIIa-R/H131, and 22% and 25% for FcyRIIa-R/R131.

However, analysis of the association between FCGR2A-R/H131 genotypes and ICU or in-hospital mortality showed that patients homozygous for the variant allele FcyRIIA-R131 had a 68% reduced risk for death relative to patients without this genotype (occurrence of homozygous genotype, 27.1 vs 10.7% for survivors vs nonsurvivors).

No linkage disequilibrium was observed between FcyRIIa-131 and IL-10-1082 alleles, and the distribution of various IL-10-1082 genotypes was not significantly different between survivors and nonsurvivors.

Regression analysis identified SAPS II (odds ratio [OR]=1.07) and Mac Cabe Score (OR=2.74) as significant independent predictors for mortality, while FcyRIIa-R/R131 was identified as a significant predictor for survival (OR=0.26).

The effect of the mutation was not significantly different in the presence or absence of meningitis infection or bacteremia.

"Future studies on IPD should include both host and pathogen genetics in well-characterized phenotypes such as pneumonia," conclude the researchers in the journal Chest.

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