Association study between killer immunoglobulin‐like receptor polymorphisms and ankylosing spondylitis disease: An updated meta‐analysis

Abstract

Background Several genetic studies have assessed the association between polymorphisms in killer immunoglobulin‐like receptors (KIR) genes and susceptibility of individuals to ankylosing spondylitis (AS), but the findings have been inconclusive and incongruous. Therefore, we conducted this meta‐analysis of all case‐control studies meeting the inclusion criteria for obtaining an exact conclusion of the effect of KIR polymorphisms on the risk of AS. Methods A systematic literature search was conducted in electronic databases, including Scopus web of science, ScienceDirect, and PubMed to find all eligible studies exploring the association between KIR polymorphisms and the risk of AS, prior to June 2017. Pooled odds ratios (OR) and their corresponding 95% CIs were used to evaluate the strength of the association between KIR polymorphisms and the risk of AS. Results A total of 16 case‐control studies, encompassed in 12 papers, with 1770 cases and 2907 healthy subjects were included in the meta‐analysis. This meta‐analysis revealed three significant positive associations of 2DS1, 2DS5, and 3DS1 with susceptibility to AS, while two significant negative associations of 2DL2 and 2DS2 with susceptibility to AS were identified. In the subgroup analysis based on human leukocyte antigen (HLA)‐B*27 positive patients and healthy subjects, results indicated that there were four significant positive associations between 2DL5, 2DS4, 2DS5, 3DS1 polymorphisms and susceptibility to AS in HLA‐B*27‐positive patients; a significant negative association of 3DL1 in HLA‐B*27‐positive patients was found. Conclusions While 2DS1, 2DS5, and 3DS1 polymorphisms increased AS risk, 2DL2 and 2DS2 polymorphisms were associated with reduced AS susceptibility.

Risk of Ankylosing Spondylitis in Patients With Endometriosis: A Population-Based Retrospective Cohort Study

“…The Killer immunoglobulin-like two-domain short-tail receptor (KIR2DS5) is a key receptor of NK cells that promotes an early immune response to infection. Previous studies indicate that the KIR2DS5 gene is a protective factor against endometriosis and AS ( 4 – 6 ). In a special case, a woman with endometriosis was diagnosed with 13 co-morbidities, including SLE and AS ( 7 ).…”

Association between Killer Immunoglobulin-like receptor genes and susceptibility to inflammatory bowel disease: An updated meta-analysis

“…Indeed, the KIR2DS1 , KIR2DS3 , KIR2DS4 , KIR2DS5 , and KIR3DS1 genes may facilitate the activation of NK cell functions, e.g., granule-mediated cytotoxicity and production of the proinflammatory cytokines IFN-γ and TNF-α, through the signaling of the KIR receptors by recognizing their corresponding ligands. In particular, KIR2DS1 is the member of the KIR gene family with the highest number of positive associations towards susceptibility to autoimmune diseases, including psoriatic arthritis [ 23 ], psoriasis vulgaris [ 24 ], and ankylosing spondylitis [ 25 ]. Also, the KIR2DS3 gene has been positively associated with susceptibility to psoriatic arthritis [ 23 ].…”

“…Also, the KIR2DS3 gene has been positively associated with susceptibility to psoriatic arthritis [ 23 ]. Furthermore, KIR2DS5 and KIR3DS1 genes have been associated with an increased risk of developing ankylosing spondylitis [ 25 ].…”

Herpesvirus Infections in KIR2DL2-Positive Multiple Sclerosis Patients: Mechanisms Triggering Autoimmunity

“…The KIRs have different numbers of the extracellular domains (2D and 3D), and a cytoplasmic tail with a different length (L (long) or S (short)) that determines protein function (inhibitory or activating, respectively) [ 10 ], with KIR2DL4 as the unique long-tailed activating KIR. The association of KIR gene polymorphisms has already been demonstrated in several autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis and inflammatory bowel disease [ 11 , 12 , 13 ]. In particular, KIR receptors might have a protective or detrimental role in autoimmune diseases due to their inhibitory or activating control of NK cells, the functions of which can be suppressed or enhanced in predisposed subjects.…”