title: GC Gene Polymorphism and Unbound Serum Retinol-Binding Protein 4 Are Related to the Risk of Insulin Resistance in Patients With Chronic Hepatitis C: A Prospective Cross-Sectional Study.
abstract: Insulin resistance (IR) is found in chronic hepatitis C (CHC) more frequently than in other chronic liver diseases.Prospective cross-sectional study to evaluate a wide multitest panel to identify factors related with IR in CHC and their possible interactions.In 76 patients with CHC we performed a series of routine laboratory analysis as well as specifically designed serum biochemical tests [retinol, retinol-binding protein 4 (RBP4), 25-OH vitamin D, Vitamin E, lipopolysaccharide-binding protein (LBP), interleukin-6 (IL-6), and cystatin C]. The single nucleotide polymorphisms rs7041 and rs4588 GC-DBP (group-specific component-Vitamin D-binding protein), rs738409 PNPLA3 (patatin-like phospholipase domain containing 3), and rs12979860 IL28B (interleukin-28 B) genes were determined. Insulin sensitivity was established with the HOMA-IR and IR was diagnosed when HOMA-IR > 3. Fibrosis staging was assessed with liver biopsy or transient elastography.After backward logistic regression analysis, independent variables associated with IR were Gc1s/Gc1s DBP phenotype, that results from the homozygous carriage of the rs7041G/rs4588C haplotype (P = 0.033); low retinol/RBP4 ratio, reflecting a greater rate of unbound RBP4 (P = 0.005); older age (P = 0.01); high serum tryglicerides (P = 0.026); and advanced (F3-F4) fibrosis stage. The AUROC provided by the multivariate model was 0.950 (95% CI = 0.906-0.993).In addition to previously known ones, the Gc1s/Gc1s phenotype variant of DBP and the unbound fraction of plasma RBP4 may be considered as factors related with the incidence, and possibly the risk, of IR in CHC patients.
authors.affiliation: From the Services of Gastroenterology (BM-M, MJD-M, JML), Clinical Laboratory (MJT, MCC), and Clinical Epidemiology (CE), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain (CF), Department of Pharmacology, Universidad de Extremadura (EG-M, GEN, JAA), Laboratory of Molecular Genetics, Hospital de Terrassa, Terrassa, Barcelona, Spain (MC), and Department of Medicine, Universidad Complutense, Madrid, Spain (MJD-M, JML).
authors.forename: Beatriz
authors.initials: B
authors.lastname: Mateos-Muñoz
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martín
authors.forename: María J
authors.initials: MJ
authors.lastname: Torrejón
authors.forename: María J
authors.initials: MJ
authors.lastname: Devesa-Medina
authors.forename: Gara
authors.initials: G
authors.lastname: Esguevillas
authors.forename: María C
authors.initials: MC
authors.lastname: Cárdenas
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernández
authors.forename: Miguel
authors.initials: M
authors.lastname: Carballo
authors.forename: José A
authors.initials: JA
authors.lastname: Agúndez
authors.forename: José M
authors.initials: JM
authors.lastname: Ladero
mesh_terms: D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics*; D054459:Elasticity Imaging Techniques; D005260:Female; D005838:Genotype; D006162:Guanylate Cyclase / Q000097:blood / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D054839:Retinol-Binding Proteins, Plasma / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma; D004247:DNA; D006162:Guanylate Cyclase