Associations of Genes for Killer Cell Immunoglobulin-like Receptors and Their Human Leukocyte Antigen-A/B/C Ligands with Abdominal Aortic Aneurysm

Abstract

Abdominal aortic aneurysm (AAA) is an immune-mediated disease with a genetic component. The multifactorial pathophysiology is not clear and there is still no pharmacotherapy to slow the growth of aneurysms. The signal integration of cell-surface KIRs (killer cell immunoglobulin-like receptors) with HLA (ligands, human leukocyte class I antigen molecules) modulates the activity of natural killer immune cells. The genetic diversity of the KIR/HLA system is associated with the risk of immune disorders. This study was a multivariate analysis of the association between genetic variants of KIRs, HLA ligands, clinical data and AAA formation. Genotyping was performed by single polymerase chain reaction with sequence-specific primers using commercial assays. Patients with HLA-A-Bw4 have a larger aneurysm by an average of 4 mm (p = 0.008). We observed a relationship between aneurysm diameter and BMI in patients with AAA and co-existing CAD; its shape was determined by the presence of HLA-A-Bw4. There was also a nearly 10% difference in KIR3DL1 allele frequency between the study and control groups. High expression of the cell surface receptor KIR3DL1 may protect, to some extent, against AAA. The presence of HLA-A-Bw4 may affect the rate of aneurysm growth and represents a potential regional pathogenetic risk of autoimmune injury to the aneurysmal aorta.

Frail Silk: Is the Hughes-Stovin Syndrome a Behçet Syndrome Subtype with Aneurysm-Involved Gene Variants?

“…Many inflammatory cells in the aneurysmal tissue produce cytokines and enzymes promoting ECM degradation, depletion of SMCs, and vessel wall injury and remodeling [ 86 ]. A genome-wide association study in BS identified genes involved in focal adhesion, MAPK signaling, transforming growth factor beta (TGF-β) signaling, ECM-receptor interaction, and complement and coagulation cascades [ 80 , 87 ], suggests their involvement in pathogenesis ( Table 2 ).…”

“…KIR3DL1/DS1 functional polymorphisms are found in BS [ 102 ]. KIR3DL1/DS1 and their HLA-class I ligands are associated with aneurysm formation in abdominal aortic aneurysms (AAA) [ 86 ].…”