title: The role of KIR genes and their cognate HLA class I ligands in childhood acute lymphoblastic leukemia.
abstract: Killer cell immunoglobulin-like receptors (KIRs), via interaction with their cognate HLA class I ligands, play a crucial role in the development and activity of natural killer cells. Following recent reports of KIR gene associations in childhood acute lymphoblastic leukemia (ALL), we present a more in-depth investigation of KIR genes and their cognate HLA ligands on childhood ALL risk. Genotyping of 16 KIR genes, along with HLA class I groups C1/C2 and Bw4 supertype ligands, was carried out in 212 childhood ALL cases and 231 healthy controls. Frequencies of KIR genes, KIR haplotypes, and combinations of KIR-HLA ligands were tested for disease association using logistic regression analyses. KIR A/A genotype frequency was significantly increased in cases (33.5%) compared with controls (24.2%) (odds ratio [OR] = 1.57; 95% confidence interval [CI], 1.04-2.39). Stratifying analysis by ethnicity, a significant difference in KIR genotype frequency was demonstrated in Hispanic cases (34.2%) compared with controls (21.9%) (OR = 1.86; 95% CI, 1.05-3.31). Homozygosity for the HLA-Bw4 allele was strongly associated with increased ALL risk exclusively in non-Hispanic white children (OR = 3.93; 95% CI, 1.44-12.64). Our findings suggest a role for KIR genes and their HLA ligands in childhood ALL etiology that may vary among ethnic groups.
authors: Department of Epidemiology and Biostatistics and.
authors: Adam J
authors: AJ
authors: de Smith
authors: Kyle M
authors: KM
authors: Walsh
authors: Martha B
authors: MB
authors: Ladner
authors: Siming
authors: S
authors: Zhang
authors: Carmen
authors: C
authors: Xiao
authors: Franziska
authors: F
authors: Cohen
authors: Theodore B
authors: TB
authors: Moore
authors: Anand P
authors: AP
authors: Chokkalingam
authors: Catherine
authors: C
authors: Metayer
authors: Patricia A
authors: PA
authors: Buffler
authors: Elizabeth A
authors: EA
authors: Trachtenberg
authors: Joseph L
authors: JL
authors: Wiemels
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005805:Genes, MHC Class I / Q000502:physiology*; D015235:HLA-B Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008024:Ligands; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology; D054340:Receptors, KIR / Q000235:genetics / Q000502:physiology*
chemical_list: D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C038652:HLA-Bw6 antigen; D008024:Ligands; D054340:Receptors, KIR