Combination of KIR 2DL2 and HLA-C1 (Asn80) confers susceptibility to type 1 diabetes in Latvians

A. Shastry, S. K. Sedimbi, R. Rajalingam, L. Nikitina-Zake, I. Rumba, H. Wigzell, C. B. Sanjeevi

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Killer immunoglobulin-like receptors (KIRs) are known to modulate natural killer (NK) and NK T-cell function by interacting with human leucocyte antigen (HLA) class I ligands on target cells. The aim of our study was to investigate the influence of KIR2D genes with their HLA-C ligands in susceptibility to type 1 diabetes. A total of 98 type 1 diabetes patients and 70 healthy subjects from Latvia were typed for KIR genes and HLA-C ligands using polymerase chain reaction-based genotyping. The HLA C1+/C2+ combination was positively, and C1-/C2+ combination was negatively, associated with type 1 diabetes. Stratification analysis of KIR/HLA-C ligand combinations showed 2DL2+/C1+, 2DL3+/C1+, and 2DS2+ /C1+ to be positively, and 2DL2-/C1- and 2DS2-/ C1- to be negatively, associated. The presence of 2DL2-HLA-C1 in the absence of 2DS1, 2DS2 confers maximum susceptibility. Absence of 2DL2 and HLA-C1 along with absence of 2DS1 and 2DS2 confer maximum protection. A hypothetical model of KIR/ligand combinations on immune responses and type 1 diabetes susceptibility is proposed. Our results suggest that a combination KIR2DL2- HLA-C1 plays a critical role in susceptibility or protection in Latvians against type 1 diabetes.

Original languageEnglish
Pages (from-to)439-446
Number of pages8
JournalInternational Journal of Immunogenetics
Volume35
Issue number6
DOIs
Publication statusPublished - Dec 2008
Externally publishedYes

Field of Science*

  • 1.6 Biological sciences
  • 3.1 Basic medicine
  • 3.2 Clinical medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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