Association of Circulating Lactoferrin Concentration and 2 Nonsynonymous LTF Gene Polymorphisms with Dyslipidemia in Men Depends on Glucose-Tolerance Status

Abstract

Background: 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.

Serum and urinary concentrations of calprotectin as markers of insulin resistance and type 2 diabetes

“…Data and samples from 298 Caucasian men were obtained from population-based prospective studies performed in two regions of Spain between 1996 and 1999: 71 subjects were recruited from the Northwest (Asturias) (20) and 227 from Northeast (Girona) (7). Two hundred and fifty (84%) eligible participants were selected at random from the census and, after a screening visit, they were invited to participate.…”

“…At 20 min, regular insulin (0.03 U/kg; Actrapid, Novo, Hellerup, Denmark) was injected as a bolus. Additional samples were obtained from a contralateral antecubital vein at times 1, 2, 3, 4, 5,6,7,8,10,12,14,16,19,20,22,23,24,25,27,30,40, 50, 60, 70, 80, 90, 100, 120, 140, 160, and 180 min. Samples were rapidly collected via a three-way stopcock connected to the butterfly needle.…”

“…In recent years, it has become evident that abnormalities in the function of the innate immune system are intrinsically linked to metabolic pathways (3). Among factors implicated in modulation of the immune response, bactericidal/permeability-increasing protein, lipopolysaccharide binding protein, complement factors, a-defensins, and lactoferrin are proteins of the innate immune system, which are also related to metabolic parameters in humans (4,5,6,7).…”

Bovine lactoferrin reduces visceral fat and liver triglycerides in ICR mice

“…Indeed, bovine LF bLF has been approved as a food additive in Japan while it is included in the generally recognized as safe category in the US. Recently, it was reported that plasma LF levels are inversely correlated with the severity of obesity as well as plasma triglyceride and free fatty acid FA levels in a clinical trial 6 , suggesting that LF may ameliorate lipid metabolism dysfunctions. Several studies have already reported the beneficial effects of bLF on lipid metabolism in animals.…”

Expression levels of JNK associated with polymorphic lactotransferrin haplotypes in human nasopharyngeal carcinoma

“…Velliyagounder et al (13) found that a Lys/Arg polymorphism (rs1126478) at position 29 in the N-terminal region of human LTF produced functional differences, and Expression levels of JNK associated with polymorphic lactotransferrin haplotypes in human nasopharyngeal carcinoma that this difference may contribute to the pathogenesis of localized juvenile periodontitis. Similarly, control individuals who were G carriers at rs1126478 had significantly lower fasting triglyceride concentrations and significantly higher high-density lipoprotein cholesterol concentrations than AA homozygotes (14). This evidence suggests that polymorphism of genes may be associated with the expression of other genes.…”