Metabolic Health in Obese Subjects—Is There a Link to Lactoferrin and Lactoferrin Receptor-Related Gene Polymorphisms?

Abstract

This study aimed to evaluate the association of genetic variants in lactoferrin (LTF) metabolism-related genes with the prevalence of metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). In total, 161 MHO and 291 MUHO subjects were recruited to the study. The following polymorphisms were genotyped: low-density lipoprotein receptor-related protein (LRP) 2 rs2544390, LRP1 rs4759277, LRP1 rs1799986, LTF rs1126477, LTF rs2239692 and LTF rs1126478. We found significant differences in the genotype frequencies of LTF rs2239692 between MHO and MUHO subjects, with the CT variant associated with lower odds of developing metabolic syndrome than the TT variant. In the total population, significant differences in body weight and waist circumference (WC) were identified between LTF rs1126477 gene variants. A similar association with WC was observed in MUHO subjects, while significant differences in body mass index and low-density lipoprotein cholesterol levels were discovered between LTF rs1126477 gene variants in MHO subjects. Besides, there were significant differences in diastolic blood pressure between LRP1 rs1799986 gene variants in MUHO subjects, as well as in WC and high-density lipoprotein cholesterol levels between LRP1 rs4759277 gene variants in MHO subjects. In conclusion, selected lactoferrin and lactoferrin receptor-related gene variants may be associated with the prevalence of metabolically healthy or metabolically unhealthy obesity.

Bioinformatics Analysis of Key Genes and Pathways for Obesity Associated Type 2 Diabetes Mellitus as a Therapeutic Target

“…ERBB2 [36], DACT1 [37], ARAP1 [38], MYH9 [39], INPPL1 [40], SARM1 [41], NOTCH1 [42], ROBO1 [43], MAPK8IP1 [44], ANK1 [45], SARM1 [46], SREBF2 [47], SIK1 [48], PASK (PAS domain containing serine/threonine kinase) [49], NOS2 [50], OAS3 [51], KL (klotho) [52], PECAM1 [53], S100A12 [54], S100P [55], BATF3 [56], PLEK (pleckstrin) [57], ALOX5 [58], ARG1 [59], CXCL8 [60], CXCR1 [61], PTAFR (platelet activating factor receptor) [62], PYGL (glycogen phosphorylase L) [63], TCF4 [64], CAMP (cathelicidin antimicrobial peptide) [65], RUNX2 [66], PLA2G2A [67], GCG (glucagon) [68], RARRES2 [69] and HAP1 [70] were involved in the genesis of type 2 diabetes mellitus. Recent studies have reported that ACHE (acetylcholinesterase) [71], FGFR3 [72], VLDLR (very low density lipoprotein receptor) [73], SHC1 [74], HDAC6 [75], CHRNA2 [76], CASR (calcium sensing receptor) [77], ELK1 [78], TYK2 [79], CIITA (class II major histocompatibility complex transactivator) [80], ZAP70 [81], GPT (glutamic--pyruvic transaminase) [82], CHI3L1 [83], AIF1 [84], MMP9 [85], ITGB2 [86], CFD (complement factor D) [87], C3AR1 [88], LGALS1 [89], CD14 [90], TIMP1 [91], TLR2 [92], LTF (lactotransferrin) [93], BRCA2 [94] and IGFBP3 [95] promotes the development of obesity. Sun et al [96] found that TRPM2 was significantly associated in obesity associated type 2 diabetes mellitus.…”

“…LGALS1 [89], CD14 [90], TIMP1 [91], TLR2 [92], LTF (lactotransferrin) [93], BRCA2 [94] and IGFBP3 [95] promotes the development of obesity. Sun et al [96] found that TRPM2 was significantly associated in obesity associated type 2 diabetes mellitus.…”

Lactoferrin, Osteopontin and Lactoferrin–Osteopontin Complex: A Critical Look on Their Role in Perinatal Period and Cardiometabolic Disorders

“…For example, an investigation conducted in 1749 French Canadians reported a significant difference in allele frequencies between subjects with and without MetS for the LTF rs2239692 polymorphism [ 105 ]. Another group of researchers documented the significant correlation between the LF rs1126477 gene variant and anthropometric parameters, allowing to propose that subjects with the CT variant of the LTF rs1126477 are endowed with a lower waist circumference compared to those with the TT variant [ 18 ]. On the other hand, male carriers of the G allele of the LF rs1126478 variant showed significantly elevated HDL-cholesterol and decreased fasting triglyceride concentrations [ 97 ].…”

Obesity, metabolic health and omics: Current status and future directions

“…Based on the results of their study, the authors suggested that the rs2331841 SNP was associated with not only obesity but also metabolic abnormalities in obese subjects. Another group of researchers focused on the lactoferrin ( LTF ) gene-related polymorphisms and observed significant differences in the genotype frequencies of LTF rs2239692 between MHO and MUO individuals[ 30 ]. The CT variant of LTF rs2239692 was found to significantly decrease the risk of MetS development in obese individuals.…”