AbstractBackground: Lactoferrin, an innate immune protein with antiinflammatory properties, shows considerable antiatherosclerosis activity in animal studies. We investigated the relationship between circulating lactoferrin, lactoferrin gene (LTF, lactotransferrin) polymorphisms, dyslipidemia, and vascular reactivity in the context of glucose-tolerance status in men.Methods: We evaluated 2 nonsynonymous LTF polymorphisms (rs1126477 and rs1126478) and measured circulating lactoferrin concentrations by ELISA under nonstressed conditions in healthy Caucasian men (n = 188) and male patients with an altered glucose tolerance (n = 202). We also studied the association of lactoferrin concentration with vascular reactivity via high-resolution ultrasound analysis of the brachial artery in a subsample of study participants.Results: Circulating lactoferrin concentration was inversely associated with fasting triglyceride concentration (r = −0.24; P = 0.001), body mass index (BMI) (r = −0.20; P = 0.007), waist-to-hip ratio (r = −0.35; P <0.001), and fasting glucose concentration (r = −0.18; P = 0.01), and directly correlated with HDL cholesterol concentration (r = 0.21; P = 0.004). Control AG heterozygotes for rs1126477 had significantly decreased fasting triglyceride concentrations (P = 0.001). Similarly, control individuals who were G carriers for rs1126478 had significantly lower fasting triglyceride concentrations (P = 0.044) and significantly higher HDL cholesterol concentrations (P = 0.028) than AA homozygotes. These associations remained significant after controlling for age, BMI, waist-to-hip ratio, fasting glucose concentration, smoking status, and alcohol intake. Circulating lactoferrin concentration was not significantly associated with endothelium-dependent vasodilatation (EDVD) in the individuals studied (n = 95); however, lactoferrin was positively associated with EDVD in obese participants with an altered glucose tolerance (r = 0.54; P = 0.04).Conclusions: We have identified associations among LTF polymorphisms, circulating lactoferrin concentration, fasting triglyceride concentration, and vascular reactivity in humans.