title: Genetic associations of killer immunoglobulin like receptors and class I human leukocyte antigens on childhood acute lymphoblastic leukemia among north Indians.
abstract: BACKGROUND
  Molecular interactions between KIRs and their cognate HLA class-I ligands, play a central role in the regulation of natural killer (NK) cell responses in malignancies. We aimed to determine the role of KIR genes and their HLA ligands in genetic predisposition of childhood acute lymphoblastic leukemia (ALL).
  
  
  METHODS
  Genotyping of 16 KIR genes, along with HLA class-I groups C1/C2 and Bw4 super-type ligands, was carried-out in 137 childhood ALL cases and 274 healthy controls.
  
  
  RESULTS
  We observed an increased incidence of activating KIRs namely; 2DS2 (OR=2.23, p=<0.001), 2DS3 (OR=1.74, p=0.011), 3DS1 (OR=2.22, p=<0.001), 2DS5 (OR=2.10, p=0.001), 2DS1 (OR=4.42, p=<0.001) and 2DS4 (OR=2.88, p=<0.001) genes in childhood ALL cases compared to controls. Frequency of BB genotype that possess 2-6 activating KIR genes was predominant in cases compared to controls (OR=2.55, p=<0.001). KIR-receptor/HLA-ligand combinations analysis revealed a moderate risk of almost 2-fold for activating KIR-ligand combinations namely; KIR2DS1-HLAC2, KIR2DS2-HLAC1 and KIR3DS1-HLABw4 in childhood ALL cases.
  
  
  CONCLUSIONS
  Our data suggests the role for KIR genes and their HLA ligands in aetiology of childhood ALL.
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India.
authors.forename: Maneesh Kumar
authors.initials: MK
authors.lastname: Misra
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India.
authors.forename: Swayam
authors.initials: S
authors.lastname: Prakash
authors.affiliation: Division of Pediatric Hematology-Oncology, Department of Pediatrics, King George's Medical University, Lucknow 226003, Uttar Pradesh, India.
authors.forename: Nirmalya Roy
authors.initials: NR
authors.lastname: Moulik
authors.affiliation: Division of Pediatric Hematology-Oncology, Department of Pediatrics, King George's Medical University, Lucknow 226003, Uttar Pradesh, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India. Electronic address: sur_ksha_agrawal@yahoo.co.in.
authors.forename: Suraksha
authors.initials: S
authors.lastname: Agrawal
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007194:India; D007694:Killer Cells, Natural / Q000502:physiology*; D008297:Male; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology*; D054340:Receptors, KIR / Q000235:genetics*
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D054340:Receptors, KIR
keywords: Acute lymphoblastic leukemia; B-cell ALL; Genetic association; HLA; KIR; T-cell ALL