Genetic variation in the Fc-ɣ receptor gene has been shown to be associated with some auto- and alloimmune diseases. Researchers investigated the relationship between the gene’s variation and protection against RBC alloimmunization in patients with sickle cell disease (SCD). In a case-control study of SCD patients from The Netherlands and France, the genetic variation in the Fc-ɣ receptor gene was compared in 142 “cases” that had alloimmunization (from at least one RBC unit) to 130 “control” patients without a history of alloimmunization after receiving at least 20 units of RBCs. Researchers typed 9 single nucleotide polymorphism (SNPs) and examined gene copy number for the Fc-ɣ receptor gene. While gene copy number was not significantly associated with protection from alloimmunization, one SNP encoding the neoclassical open reading frame in the Fc-ɣ receptor gene (FCGR2c.nc-ORF) was associated with protection from RBC alloimmunization in patients with SCD (odds ratio=0.26; 95% CI, 0.11-0.64; p=0.003). This association was strengthened after excluding cases of alloimmunization with Rh or K1 antibodies. Further researcher is needed to confirm these results and understand the mechanism of the protection.