Flesch B K, Nikolaus S, El Mokhtari N E, Schreiber S, Nebel A
Institute of Transfusion Medicine, University Hospital Schleswig-Holstein, Kiel, Germany.
Int J Immunogenet. 2006 Aug;33(4):277-9. doi: 10.1111/j.1744-313X.2006.00613.x.
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.
FCGR2A基因中的功能性单核苷酸多态性rs1801274（His131Arg）会影响hIgG2的结合效率，hIgG2是针对肺炎链球菌和流感嗜血杆菌等包膜细菌产生的主要同种型。与具有His131等位基因的受体不同，FcγRIIa-Arg131与hIgG2的结合能力较差，并且已证明该变体的携带者更容易死于细菌性肺炎或脑膜炎。由于菌血症性肺炎是老年人死亡的主要原因之一，我们推测Arg131变体可能是老年人死亡的主要因素。我们分析了一组408名德国百岁老人以及分别为60 - 75岁和18 - 49岁的两个德国年轻人样本中的FCGR2A-His131Arg多态性。在三个年龄组之间，无论是等位基因水平还是基因型水平，均未观察到统计学上的显著差异。显然，活到老年的能力在很大程度上不受基于FCGR2A的免疫反应的遗传决定效力的影响。然而，FCGR2A-131Arg携带者清除包膜细菌的能力严重下降，这显然必须由另一种机制来补偿，可能涉及其他遗传生存因素。
