Three SNPs linked to MS pathology-associated genes showed a significant association with either proportion of active lesions (rs3130253/MOG), incidence of cortical gray matter lesions (rs1064395/NCAN) or the proportion of remyelinated lesions (rs5742909/CTLA4).
<b>Interpretation:</b> This is an initial exploration of the utility of CTLA-4, PD-1, TIM-3, LAG-3, and TIGIT expression levels as prognostic indicators in untreated, recently diagnosed multiple sclerosis.
In this case–control study (336 multiple sclerosis (MS) patients and 322 controls) we investigated the possible association of eleven polymorphisms in CD28, CTLA-4, CD80 and CD86 genes with susceptibility to MS and/or its progression.
Single-nucleotide polymorphisms (SNPs) of CTLA-4 gene are known to be associated with susceptibility to several autoimmune diseases, including multiple sclerosis (MS).
Here we describe linked intronic variants of MGAT5 that are associated with reduced N-glycan branching, CTLA-4 surface expression and MS (p=5.79×10(-9), n=7,741), the latter additive with the MGAT1, IL2RA and IL7RA MS risk variants (p=1.76×10(-9), OR=0.67-1.83, n=3,518).
Multiple environmental factors (vitamin D(3) deficiency and metabolism) converge with multiple genetic variants (IL-7RA, IL-2RA, MGAT1, and CTLA-4) to dysregulate Golgi N-glycosylation in MS, resulting in T cell hyperactivity, loss of self-tolerance and in mice, a spontaneous MS-like disease with neurodegeneration.
No significant differences were observed in CTLA-4 +49 A or G allele distribution between patients and controls, indicating that this polymorphism does not influence susceptibility to MS in the surveyed populations.
In spite of some previous reports, this study did not confirm any significant association with alleles and genotypes of SNPs of the CTLA4 in Iranian MS patients.
After Bonferroni correction, the results provide preliminary evidence that CTLA4 genetic variation at -1661 locus may render Iranian individuals to be more susceptible to MS, whereas harboring TACA haplotype might be protective.
A study was undertaken to evaluate the association of the CTLA-4 gene polymorphisms -319C/T, +49A/G, (AT)(n), CT60A/G and Jo31G/T with the levels of membrane CTLA-4 (mCTLA-4) and cytoplasmic CTLA-4 (cCTLA-4) in CD4(+) T lymphocytes from patients with multiple sclerosis (MS) and with susceptibility to MS, and the course of the disease.
A case-control association study was conducted in German, Hungarian and Polish multiple sclerosis (MS) patients and regional control individuals for the CTLA4 CT60 and +49A/G polymorphisms.
As a non-European patient population, our results are consistent with the major previous studies showing no significant associations between CTLA4 exon 1 polymorphism and neither MS nor any of its subtypes.
We have investigated whether the A49G single nucleotide polymorphism (SNP) genotype of the CTLA-4 gene influenced the development of MS in Southern Australians as well as the interaction of this SNP with the DRB1*15 haplotype.
The involvement of CTLA4 in the pathogenesis of MS may be subtle and related to the functional changes in its pathway rather than predisposing genetic polymorphisms.
The involvement of CTLA4 in the pathogenesis of MS may be subtle and related to the functional changes in its pathway rather than predisposing genetic polymorphisms.
Demonstration of prolonged proliferation in patient samples containing the GG genotypes and altered CD152 surface expression was also not demonstrated suggesting that the CD152 exon 1 position 49 A/G dimorphism does not contribute significantly to the development of MS in this patient population.
Our hypothesis is that the increase in Fas and CTLA4 molecules in MS patients may lead to lymphocyte apoptosis, which suggests possible mechanisms underlying the therapeutic response to IFN-beta.
Our results suggest that CTLA-4 gene polymorphisms are neither conclusively related to susceptibility nor to the clinical characteristics of MS, especially in Japanese patients with conventional/classical form and clinical features identical to those of their counterparts in Western countries.