Killer immunoglobulin-like receptors and HLA C1/C2 genes diversities and susceptibility to acute myeloid leukemia in Saudi Arabian patients

Abstract

ObjectiveNatural Killer cells activation depends on the interaction with killer cell immunoglobin-like receptors (KIRs), which bind the peptide-binding region of several class-I Human Leukocyte Antigens (HLA class-I). In addition, KIR and HLA loci are highly polymorphic and display significant variation between individuals. MethodsWe attempted to investigate the association of 16 KIR complexes and the HLA-C1 and C2 ligands to the genetic predisposition and development of Acute Lymphoblastic leukemia (AML) in Saudi Arabian patients. We genotyped 16 KIR genes for 100 patients with Acute Lymphoblastic leukemia and 114 healthy controls, and all samples were considered for evaluating combined KIR-HLA C1/C2 associations. ResultsKIR genotype frequency differed significantly between AML patients and healthy controls. KIR2DL1, KIR2DL5, and KIR2DS2 increased significantly in patients than in controls. The 2DL5 gene contributed to the highest risk of AML (OR = 2.9906, p < 0.00059), followed by 2DS2 (OR = 1.8068; p < 0.039). However, the incidence of KIR 2DL3, KIR2DS4, and KIR2DL2 was significantly elevated in healthy controls compared to myeloid leukemia patients. The distributions of HLA-C1 and C2 ligands were not significantly different between patients and controls. Analyses of different combinations of KIR/HLA class I ligand profile show that the frequency of KIR2DL3 + in the presence of the allotype C1 was decreased among AML patients compared to controls. Similarly, KIR2DL3 and KIR2DL2/2DL3, when combined with their respective ligands, HLA-C2/C1, were significantly less prevalent in AML patients when compared to controls. ConclusionOur data suggested a potential predictive role for a specific KIR genotype, and HLA-I encoding genes to AML risk.