Background: The myelin basic protein (MBP) gene may confer genetic susceptibility to multiple sclerosis (MS). The association of MS with alleles of the (TGGA)n variable number tandem repeat (VNTR) 5' to the MBP gene is the subject of conflicting reports.
Objective: To study possible MS association with VNTR alleles of MBP gene in ethnic Italians and ethnic Russians.
Methods: Two hundred sixty-nine unrelated patients with definite MS and 385 unrelated healthy control subjects from Italy and Russia were genotyped for the MBP VNTR region and for the human leukocyte antigen (HLA) class II DRB1 gene. The phenotype, allele, and genotype frequencies for two groups of MBP alleles were determined. Patients and control subjects were stratified according to HLA-DRB1 phenotypes.
Results: The distribution of MBP alleles and genotypes in the two ethnic groups, including both MS patients and control subjects, was very similar. When MS patients and healthy control subjects were stratified according to HLA-DRB1 phenotypes, a significant association of MS with MBP alleles was found only in the DR4- and DR5-positive subgroups. A significant association with MBP alleles was also observed in the nonstratified groups, owing mainly to the contribution of the DR4- and DR5-positive individuals.
Conclusion: Polymorphism of the MBP or another gene in its vicinity appears to contribute to the etiology of MS for the subgroups of DR4- and DR5-positive Italians and Russians.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1212/01.wnl.0000079372.54703.a8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Novel Immunoliposome Technology for Enhancing the Activity of the Agonistic Antibody against the Tumor Necrosis Factor Receptor Superfamily.
Mol Pharm
September 2018
Daiichi Sankyo Co., Ltd. , 1-2-58 Hiromachi , Shinagawa-ku, Tokyo 140-8710 , Japan.
We have developed a technology for efficiently enhancing the anticancer apoptosis-inducing activity of agonistic antibodies against the tumor necrosis factor receptor (TNFR) superfamily by the formation of immunoliposomes. To induce apoptosis in cancer cells, agonistic antibodies to the TNFR superfamily normally need cross-linking by internal immune effector cells via the Fc region after binding to receptors on the cell membrane. To develop apoptosis-inducing antibodies that do not require the support of cross-linking by immune cells, we prepared immunoliposomes conjugated with TRA-8, an agonistic antibody against death receptor 5 (DR5), with various densities of antibody on the liposome surface, and evaluated their activities.
View Article and Find Full Text PDFSynthetic ligands of death receptor 5 display a cell-selective agonistic effect at different oligomerization levels.
Oncotarget
October 2016
Institut de Biologie Moléculaire et Cellulaire, UMR 3572, Laboratoire d'Immunopathologie et Chimie Thérapeutique, Strasbourg 67084, France.
DR4 (Death Receptor 4) and DR5 (Death Receptor 5) are two potential targets for cancer therapy due to their ability to trigger apoptosis of cancer cells, but not normal ones, when activated by their cognate ligand TRAIL (TNF related apoptosis-inducing ligand). Therapies based on soluble recombinant TRAIL or agonist antibodies directed against one of the receptors are currently under clinical trials. However, TRAIL-R positive tumor cells are frequently resistant to TRAIL induced apoptosis.
View Article and Find Full Text PDFDeath receptor 5 and neuroproliferation.
Cell Mol Neurobiol
March 2012
Institute of Neurobiology, College of Life Science, Henan University, Kaifeng 475004, Henan, People's Republic of China.
Tumor necrosis factor-related apoptosis-inducing ligand or Apo2 ligand is a member of the tumor necrosis factor superfamily of cytokines that induces apoptosis upon binding to its death domain-containing transmembrane receptors, death receptors 4 and 5 (DR4, DR5). However, DR5 is also expressed in the developing CNS where it appears to play a role unrelated to apoptosis, and instead may be involved in the regulation of neurogenesis. We report on the distribution of DR5 expression in mouse hippocampus, cerebellum, and rostral migratory stream (RMS) of olfactory bulb from embryonic (E) day 16 (E16) to postnatal (P) day (P180).
View Article and Find Full Text PDFResveratrol sensitizes melanomas to TRAIL through modulation of antiapoptotic gene expression.
Exp Cell Res
March 2008
Center for Radiological Research, Columbia University, New York, NY 10032, USA.
Although many human melanomas express the death receptors TRAIL-R2/DR5 or TRAIL-R1/DR4 on cell surface, they often exhibit resistance to exogenous TRAIL. One of the main contributors to TRAIL-resistance of melanoma cells is upregulation of transcription factors STAT3 and NF-kappaB that control the expression of antiapoptotic genes, including cFLIP and Bcl-xL. On the other hand, the JNK-cJun pathway is involved in the negative regulation of cFLIP (a caspase-8 inhibitor) expression.
View Article and Find Full Text PDFProgression in melanoma is associated with decreased expression of death receptors for tumor necrosis factor-related apoptosis-inducing ligand.
Hum Pathol
October 2006
Discipline of Pathology, Faculty of Medicine, University of Sydney, Sydney, New South Wales 2006, Australia.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in melanoma by interaction with death receptors TRAIL-R1 (DR4) or TRAIL-R2 (DR5) on melanoma cells or resists apoptosis by interaction with decoy receptors TRAIL-R3 (DcR1) or TRAIL-R4 (DcR2). Studies on cell lines suggest that there is a wide variation in TRAIL death receptor expression; however, their expression on excised human melanoma is not well documented. In view of this, we studied death receptor expression on melanomas using monoclonal antibodies specific for these receptors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!