Blackwell Publishing Ltd. 

FCGR2A Arg131 Variant Is Not a Major Mortality Factor in the Elderly: Evidence from a German Centenarian Study

B. K. Flesch,* S. Nikolaus, N. E. El Mokhtari, S. Schreiber & A. Nebel

Encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae cause pneumonia, meningitis, otitis media, and acute sinusitis in addition to other serious infectious diseases. Previous studies have shown that variation in the FCGR2A gene, which codes for the Fc receptor for human immunoglobulin G (Fc RIIa), influences susceptibility to infections caused by these bacteria. A functional single nucleotide polymorphism (SNP) in the FCGR2A gene (rs1801274) results in a histidine to arginine exchange at codon 131 (His131Arg). Of the two variants, only Fc RIIa-His131 can efficiently bind IgG2, which is the main immunoglobin type produced in response to bacterial polysaccharides and encapsulated bacteria.

Previous studies have suggested that individuals positive for the Arg131 variant are more susceptible to bacterial pneumonia or meningitis. As bacteraemic pneumonia is one of the leading causes of death in elderly individuals, we hypothesized that the Arg131 variant could be a major mortality factor in the old. However, our analysis of the FCGR2A-His131Arg polymorphism in a group of 408 German centenarians and two samples of younger Germans aged 60-75 and 18-49 years respectively did not show any statistically significant differences between the three age groups at either the allele or genotype level. Apparently, genetic determinants do not play a significant role in reaching old age.

In elderly individuals, pneumonia is a major threat to health and survival. The death rate of pneumonia is 25-fold higher for people between 65 and 74 years, and for individuals older than 84 years it is even 458-fold higher than that for 25- to 44-year-olds. If the Fc RIIa-His131 allele indeed has such a key role in the defense of polysaccharide-coated bacteria, we would expect the Arg131 polymorphic form to decrease in frequency as a population ages, with carriers of the unfavorable variant being more prone to succumb to bacteraemic pneumonia. However, our findings suggest that the ability to reach old age is largely unaffected by the genetically determined efficacy of the FCGR2A-based immune response. The severely reduced ability of FCGR2A-131Arg carriers to eliminate encapsulated bacteria must apparently be compensated by an alternative mechanism, possibly involving other genetic survival factors.

Bacteraemic pneumonia is the fourth leading cause of death in elderly individuals. More than half of all bacterial pneumonia infections at age 60 and above are caused by Streptococcus pneumoniae and Haemophilus influenzae combined. We examined three different age groups (adult, elderly, and centenarian) for the non-synonymous mutation rs1801274 (His131Arg) in the FCGR2A gene. The unrelated and healthy study participants were drawn anonymously from population-based samples. The three samples were matched by ethnic ancestry (all Germans) and sex ratio (80% females vs. 20% males).