The FCGR2A— Arg131 variant is no major mortality factor in the elderly — evidence from a German centenarian study

Abstract

The functional single nucleotide polymorphism rs1801274 in the FCGR2A gene (His131Arg) influences the efficiency of hIgG2 binding, the main isotype produced in response to encapsulated bacteria like Streptococcus pneumoniae and Haemophilus influenzae. In contrast to the receptor with the His131 allele, FcgammaRIIa-Arg131 binds hIgG2 poorly and carriers of this variant have been shown to be much more susceptible to succumb 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. We analysed 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. No statistically significant differences were observed between the three age groups, neither at the allele nor at the genotype level. Apparently, the ability to reach old age is largely unaffected by the genetically determined efficacy of the FCGR2A-based immune response. However, 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.

Decanucleotide insertion polymorphism of F7 significantly influences the risk of thrombosis in patients with essential thrombocythemia

“…The genotype frequencies of the NOS3 polymorphism compared well to published data (11). Regarding the FCGR2A His131Arg genotype frequencies we observed twice as many subjects with a homozygous genotype but the same rate of patients with a heterozygous genotype compared to genotype frequencies in a large German study (30).…”

Aetiology of Community-Acquired Pneumonia and the Role of Genetic Host Factors in Hospitalized Patients in Cyprus

“…FcγRII is a surface receptor found on immune cells, with the variant FcγRIIa (CD32a) mainly expressed on neutrophils, macrophages, and dendritic cells [ 24 ]. The CD32a receptor is the only one capable of interacting with IgG2, which is specifically directed against encapsulating bacteria [ 25 ]. The rs1801274 polymorphism has been shown to have a reduced affinity to IgG2, with macrophages carrying the variant alleles of the polymorphism having a reduced phagocytosis of IgG2-opsonized particles [ 26 ].…”

Invasive Bacterial Infections in Subjects with Genetic and Acquired Susceptibility and Impacts on Recommendations for Vaccination: A Narrative Review

“…Disorders that influence the efficiency of IgG2 binding, the main isotype produced in response to encapsulated bacteria may also increase susceptibility to Hi infections. For example, the His131Arg allele encoding Fcgamma RIIa receptor (rs1801274) binds IgG2 poorly, and therefore, increases the risk of Hi infections [46]. Patients with a single nucleotide polymorphism (SNP) in the TIRAP gene (Toll-interleukin 1 receptor domain containing adaptor protein, an adapter molecule associated with Toll-like receptor) (rs1893352) was reported to be strongly associated with non-meningitis cases of Hib in vaccinated children.…”