Associations of Genes for Killer Cell Immunoglobulin-like Receptors and Their Human Leukocyte Antigen-A/B/C Ligands with Abdominal Aortic Aneurysm.
Joanna DubisWanda Niepiekło-MiniewskaNatalia JędruchniewiczMaciej SobczyńskiWojciech WitkiewiczNorbert ZapotocznyPiotr KuśnierczykPublished in: Cells (2021)
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.
Keyphrases
- abdominal aortic aneurysm
- cell surface
- genetic diversity
- endothelial cells
- coronary artery
- genome wide
- single cell
- high throughput
- cell therapy
- pulmonary artery
- poor prognosis
- stem cells
- gene expression
- peripheral blood
- big data
- smoking cessation
- machine learning
- pulmonary hypertension
- deep learning
- copy number
- genome wide identification