Interleukin-6 and interleukin-10 gene polymorphism, endothelial dysfunction, and postoperative prognosis in patients with peripheral arterial disease

Abstract

Objectives: The aim of this study was to evaluate the association between interleukin (IL)-6 and IL-10 gene polymorphism and the short-term risk of postoperative cardiovascular events in patients with peripheral artery disease receiving elective surgery and also to evaluate the endothelial function.

Methods and results: We determined preoperatively IL-6 gene polymorphism (-174 G/C and nt565 G/A), IL-10 polymorphism (-1082G/A, -819C/T, -592C/A), and brachial artery vasodilatation using ultrasound in 48 patients undergoing vascular surgery. Eight patients (16.7%) developed over a period of 30 days cardiovascular events (cardiovascular death, resuscitated cardiac arrest, acute myocardial infarction, unstable angina, stroke). Cardiovascular events were more frequent in the subgroups of patients with genotypes associated with high serum levels of IL-6: -174CC (57.14% vs 12.5% for -174GC genotype and 8% for -174GG, P = .007) and nt565AA (50% vs 17.6% for nt565GA genotype and 8% for nt565GG genotype, P = .021) and in subgroups with haplotypes associated with low serum levels of IL-10: ATA (57.14% vs 14.8% for haplotype ACC and 7.4% for GCC, GCA, GTA, GTC haplotypes, P = .004). Flow-mediated dilatation was significantly lower in patients with IL-6 -174CC genotype (7.05% +/- 1.49% vs 8.41% +/- 1.9% for IL-6 -174GC and 9.42% +/- 2.46% for IL-6 -174GG, P = .009) and IL-6 nt565AA genotype (7.14 +/- 1.61% vs 8.49% +/- 1.91% for IL-6 nt565GA and 9.42% +/- 2.46% for IL-6 nt565GG, P = .018) and in patients with IL-10ATA haplotype (6.45% +/- 0.57% vs 9.13% +/- 2.52% for IL-10ACC and 9.24% +/- 2.09% for IL-10 GCC/GCA/GTA/GTC, P = .004) respectively.

Conclusions: IL-6 -174CC and nt565AA genotypes and IL-10ATA haplotypes are correlated with a high short-term risk of acute postoperative cardiovascular events in patients with peripheral artery disease receiving elective surgical revascularization and with endothelial dysfunction in these patients.