TRAF1-C5

Background. Previous studies reported associations between specific alleles of non-HLA immunoregulatory genes and higher fatigue scores in patients with primary biliary cirrhosis (PBC). Aim. To study the relationship between variables of health-related quality of life (HRQoL) and single nucleotide polymorphisms of TRAF1-C5, a member of the tumor necrosis factor receptor family. Patients and Methods. TRAF1-C5 gene polymorphisms, rs2900180 and rs3761847, were analysed in 120 Caucasian PBCs. The HRQoL was assessed with SF-36, PBC-40, and PBC-27 questionnaires. Results. We found a negative association between TT genotype of rs2900180 and SF-36’s domains vitality (P<0.05), mental health (P<0.05), and mental component summary score (P<0.05). GG homozygotes of rs3761847 had lower vitality (P<0.05), mental health (P<0.05), mental component summary score (P<0.05) and impairment of social functioning (P<0.01). Allelic analysis has shown that T allele of rs2900180 and G allele of rs3761847 related to SF-36’s vitality (P<0.05 and P<0.01), social functioning (P<0.05 and P<0.05), mental health (P<0.01 and P<0.05), and mental component summary score (P<0.01 and P<0.05), respectively. Genotyping and allelic analysis did not reveal correlation with PBC-40 and PBC-27 domains. Conclusion. The association between rs2900180 and rs3761847 polymorphisms and HRQoL variables indicates that TRAF1 is involved in the induction of impaired QoL in PBC

Monoclonal antibodies against the renal Na⁺-D-glucose cotransporter. Identification of antigenic polypeptides and demonstration of functional coupling of different Na⁺-cotransport systems

Eight monoclonal antibodies are described which are directed against the renal Na+-D-glucose cotransporter. In porcine renal brush-border membranes, the antibodies either bind to one or to three polypeptides which have been identified as components of the Na+-D-glucose cotransporter (Neeb, M., Kunz, U., and Koepsell, H., (1987) J. Biol. Chem. 262, 10718-10727). Their molecular weights and isoelectric points are 75,000 and pH 5.5, 60,000 and pH 5.2, and 47,000 and pH 5.4. Six antibodies were able to influence Na+-dependent D-glucose uptake and/or Na+-dependent high affinity phlorizin binding. In the presence of Na+, the binding of all antibodies to native membrane proteins was altered by D-glucose but not by D-mannose. Since this effect was observed with D-glucose concentrations less than 1 x 10(-8) M, a high affinity D-glucose-binding site on the D-glucose transporter has been implied. Some of the antibodies probably interact also with other Na+-coupled transporters since their binding was altered by micromolar concentrations of L-lactate, L-alanine, or L-glutamate but not by the nontransported control substances D-alanine and D-glutamate. L-lactate increased the binding of one antibody in the absence but not in the presence of D-glucose. Effects of L-lactate and L-alanine on the binding of another antibody were only observed when D-glucose was present. Thus, some epitopes on the Na+-D-glucose cotransporter are altered by D-glucose and also by substrates of other Na+ cotransporters. This finding suggests functional coupling of different Na+-cotransport systems