In addition to celiac disease (CD), type I diabetes, Grave's disease, rheumatoid arthritis and multiple sclerosis have all demonstrated associations to the A/G single nucleotide polymorphism (SNP) in exon 1, position +49 of the CTLA4 gene.
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.
Thus, we propose that the susceptibility-influencing role of CTLA4 in MS may be related to genotypically conditioned promoter function, whereby high gene expression may decrease the risk of disease.
In contrast, CTLA-4 blockade had less effect in patients with MS, suggesting that at least two regulatory mechanisms may be impaired in these individuals.
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.
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.
We describe meta-analytical approaches that provide additional statistical power necessary for detecting such loci and further apply this approach to evaluate the association of a CTLA-4 variant with MS. Lastly, we review recent important advances in our understanding of the patterns of genetic variation in the human genome and speculate about how these advances will aid in future studies of the genetic causes of MS.
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.
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).
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.
Because soluble CD28 and CTLA-4 molecules might affect T cell activation, our findings suggest an additional means whereby IFN-beta therapy might exert its immunomodulatory effects in multiple sclerosis (MS).
A single-nucleotide polymorphism (SNP) in exon 1 of CTLA4 is associated with susceptibility to several autoimmune diseases, including multiple sclerosis (MS).
Single-nucleotide polymorphisms (SNPs) of CTLA-4 gene are known to be associated with susceptibility to several autoimmune diseases, including multiple sclerosis (MS).
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.
Functional polymorphisms of the genes for interleukin-10 (IL-10; promoter position -1082), chemokine receptor-5 (CCR5 32 bp deletion), tumor necrous factor-alpha (TNFalpha promoter position -308) and cytotoxic T-lymphocyte antigen-4 (CTLA-4 exon 1 position 49) were investigated for possible influence on susceptibility and outcome of multiple sclerosis (MS).