Aims: Atherosclerosis, a chronic inflammatory disease, is the most important cause of cardiovascular morbidity and mortality. Interleukins (ILs) play a crucial role in balancing anti- and pro-inflammatory stimuli. The aim of our study was to investigate the association between intima-media thickness (IMT) and genetic variation in ILs.

Methods: In 360 participants (mean age 41.7 years; 52.8% women), randomly recruited from a Flemish population, we measured carotid (n=348), femoral (n=355) and brachial (n=355) IMT using ultrasound. After amplifying DNA fragments, we genotyped for IL-1a 549C/T, IL-1b 4336C/T, , IL-4 582C/T, IL-4 receptor (IL-4R) 398A/G, IL-4R 1682T/C, IL-5R 482G/A, IL-6 589G/C, IL-6 987G/C, IL-9 4244C/T, IL-10 8700C/A polymorphisms and IL-13 4045C/T. We applied a mixed model to assess phenotype-genotype associations while accounting for relatedness and covariables.

Results: In multiple regression analyses, IMT in all arteries increased with age, and brachial IMT increased with systolic blood pressure. Women had higher femoral IMT than men. With adjustments applied for these covariables, carotid IMT was higher in IL-1a C allele carriers (0.624±0.016 vs 0.549±0.038, P=0.045) and in IL-4Rα GG homozygotes (0.655±0.022 vs 0.603±0.016, P=0.027). IL-5 GG homozygotes had lower femoral IMT than their A allele counterparts did (0.665±0.022 vs 0.728±0.027, P=0.020). Carotid and brachial IMT were lower in IL-9 CC homozygotes than in T allele carriers (0.610±0.016 vs 0.671±0.029, P=0.020; 0.313±0.008 vs 0.348±0.016, P=0.027).

Conclusions: In line with experimental studies in animals and high heritability of carotid IMT, we demonstrated that IMT was associated with genetic variations in several interleukins components.