Genetic Variation in Immunoglobulin G Receptor Affects Survival After Lung Transplantation

Abstract

Chronic rejection remains the most important complication after lung transplantation (LTx). There is mounting evidence that both rheumatoid arthritis and chronic rejection share similar inflammatory mechanisms. As genetic variants in the FCGR2A gene that encodes the immunoglobulin gamma receptor (IgGR) have been identified in rheumatoid arthritis, we investigated the relationship between a genetic variant in the IgGR gene and chronic rejection and mortality after LTx. Recipient DNA from blood or explant lung tissue of 418 LTx recipients was evaluated for the IgGR (rs12746613) polymorphism. Multivariate analysis was carried out, correcting for several co-variants. In total, 216 patients had the CC-genotype (52%), 137 had the CT-genotype (33%) and 65 had the TT-genotype (15%). Univariate analysis demonstrated higher mortality in the TT-genotype compared with both other genotypes (p<0.0001). Multivariate analysis showed that the TT-genotype had worse survival compared with the CC-genotype (hazard ratio [HR]=2.26, p=0.0002) but no significance was observed in the CT-genotype (HR=1.32, p=0.18). No difference was seen for chronic rejection. The TT-genotype demonstrated more respiratory infections (total, p=0.037; per patient, p=0.0022) compared with the other genotypes. A genetic variant in the IgGR is associated with higher mortality and more respiratory infections, although not with increased prevalence of chronic rejection, after LTx.