The effect of genetic variants affecting NK cell function on cardiovascular health and the burden of CMV

Renal transplant recipients (RTR) display high burdens of cytomegalovirus (CMV) and accelerated cardiovascular change. NK cells can control CMV and may contribute to vascular pathologies. Polymorphisms in genes encoding the inhibitory receptor LILRB1 and its ligand HLA-G, and the activating receptor NKG2C may illuminate the role of NK cells in vascular health and CMV immunity. We assessed 81 healthy adults and 82 RTR >2 years after transplantation. RTR had higher humoral and T-cell responses to CMV, and impaired vascular health. A 14bp indel in HLA-G associated with increased flow-mediated dilatation of the brachial artery. The T allele of LILRB1 rs1061680 associated with increased carotid intimal media thickness (cIMT) in RTR and controls. A 16 kb deletion encompassing the NKG2C gene associated with lower cIMT values and higher humoral and T-cell responses to CMV. Hence all polymorphisms tested had small but discernable effects on vascular health. The NKG2C deletion may act via CMV.