Killer immunoglobulin receptor genes and their HLA-C ligand are associated with Type 1 diabetes in an Eastern Indian population

Diabet Med. 2016 Jan;33(1):91-6. doi: 10.1111/dme.12815. Epub 2015 Jul 2.

Abstract

Aim: Killer immunoglobulin-like receptors (KIRs) and their interaction with HLA class I ligands have been shown to be associated with Type 1 diabetes mellitus. The aim of our study was to investigate the influence of KIR genes and their HLA-C ligands for susceptibility to Type 1 diabetes in patients from Eastern India.

Methods: A total of 135 patients with Type 1 diabetes and 98 healthy subjects from Eastern India were typed for KIR genes and HLA-C ligands using PCR-based genotyping. The frequencies of these genes were compared between patients and controls.

Results: Comparison of KIR genes between Type 1 diabetes patients and healthy subjects revealed significantly different frequencies of KIRs 2DL2 and 2DS4. The presence of HLA-C1 was negatively associated with disease. The presence of both HLA-C1 and -C2 showed a negative association with Type 1 diabetes, whereas the absence of C1 and presence of C2 was positively associated with disease. Stratification analysis of HLA-C ligands and KIRs showed significant associations between Type 1 diabetes and 2DL2+/C1-, 2DL2-/C1+, 2DL3+/C1+, 2DL3+/C1- and 2DS2+/C1-.

Conclusions: Our results suggest that the interaction of KIRs with HLA-C ligands are significant and certain combinations contribute to susceptibility to and protection against Type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / metabolism
  • Disease Susceptibility
  • Gene Expression Regulation
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • HLA-C Antigens / blood*
  • HLA-C Antigens / genetics
  • HLA-C Antigens / metabolism
  • Humans
  • India
  • Ligands
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / metabolism*
  • Polymorphism, Genetic*
  • Receptors, KIR / agonists
  • Receptors, KIR / blood
  • Receptors, KIR / genetics*
  • Receptors, KIR / metabolism
  • Receptors, KIR2DL2 / agonists
  • Receptors, KIR2DL2 / blood
  • Receptors, KIR2DL2 / genetics*
  • Receptors, KIR2DL2 / metabolism
  • Receptors, KIR2DL3 / agonists
  • Receptors, KIR2DL3 / blood
  • Receptors, KIR2DL3 / genetics*
  • Receptors, KIR2DL3 / metabolism

Substances

  • HLA-C Antigens
  • KIR2DL2 protein, human
  • KIR2DL3 protein, human
  • KIR2DS4 protein, human
  • Ligands
  • Receptors, KIR
  • Receptors, KIR2DL2
  • Receptors, KIR2DL3