Osteopontin as an early predictor of atherosclerosis in attack-free Familial Mediterranean fever patients

Abstract

Familial Mediterranean fever (FMF) is an autoinflammatory disease that is associated with endothelial dysfunction and atherosclerosis. Osteopontin which is a multifunctional protein involved in the modulation of inflammatory processes may contribute to the development of atherosclerosis in FMF patients. Therefore, this cross-sectional study investigated the relationship of osteopontin with carotid intima media thickness (CIMT) and atherogenic indices in patients with FMF. Serum osteopontin levels, CIMT, Castelli risk index I and II, plasma atherogenic index (PAI), non - high-density lipoprotein cholesterol, and atherogenic coefficient (AC) in 64 attack-free FMF patients were compared with levels in 23 healthy control subjects. The serum osteopontin level, CIMT, Castelli risk index I, AC and PAI were significantly higher, and high-density lipoprotein cholesterol was significantly lower in FMF patients (P < .001, P < .001, P = .045, P = .016, P = .045, and P = .024; respectively). There were significant positive correlations between osteopontin and CIMT, PAI, AC, and Castelli risk index I (R = 0.580, R = 0.259, R = 0.233, R = 0.277; respectively) and there was significant negative correlation between osteopontin and high-density lipoprotein cholesterol (r= −0.309). Patients who had homozygote mutations had significantly higher osteopontin, PAI, Castelli risk index I and II level. The current study is the first to demonstrate significantly increased serum osteopontin levels in attack-free FMF patients compared with healthy controls. It was also associated with CIMT and many atherogenic indices. This finding provides a new experimental basis to understand the pathogenesis of inflammation-induced atherosclerosis in FMF patients. Furthermore, patients who had homozygote mutations had worse atherogenic indices than those with heterozygote mutations.