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Analysis of Killer Cell Immunoglobulin-Like Receptors (Kirs) and Their Hla Ligand Genes Polymorphisms in Iranian Patients With Systemic Sclerosis Publisher Pubmed



Mahmoudi M1 ; Fallahian F2 ; Sobhani S1 ; Ghoroghi S1 ; Jamshidi A1 ; Poursani S1 ; Dolati M2 ; Hosseinpour Z1 ; Gharibdoost F1
Authors
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Authors Affiliations
  1. 1. Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Kargar Ave, P.o. box: 1411713137, Tehran, Iran
  2. 2. Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran

Source: Clinical Rheumatology Published:2017


Abstract

Genetic factors have a great role in the pathogenesis of autoimmune diseases by cooperating with environmental stimuli. Killer immunoglobulin-like receptors (KIRs) are cell surface proteins on NK cells whose association with major histocompatibility complex-I regulates their killing function. The aim of this study was to provide information on the possible association between KIR and human leukocyte antigen (HLA) genes with systemic sclerosis disease in Iranian population. A total of 279 systemic sclerosis patients and 451 healthy controls were enrolled in this case-control study in order to determine the presence or absence of 19 KIR genes and 6 specific HLA class I ligands. DNA was analyzed by polymerase chain reaction using the specific sequence primer method (PCR-SSP). Among 11 discovered KIR genotypes, 6 genotypes showed a considerable role and 4 genotypes could preclude the risk of systemic sclerosis (SSc) disease. The gene-gene interactions were also analyzed, and significant confounding effects were seen between involved genes in these two combinations: “KIR3DL1; HLA-BW4-Thr80” and “KIR3DL1 -HLA-BW4-A1.” None of single KIR genes showed significant effect on the risk of SSc. We conclude that there is an important relationship between KIR genes and their HLA ligands with incidence rate of systemic sclerosis in Iranian population. The powerful role of a number of discovered KIR/HLA compounds such as activating KIR genotype 3 and HLA-BW4-A1 confirmed the provocative hypothesis of the interplay between activating or inhibitory KIR genes with HLA ligands as a critical index of systemic sclerosis predisposition. © 2017, International League of Associations for Rheumatology (ILAR).
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