Abstract
We have investigated whether three intragenic polymorphisms of the CTLA-4 gene, a C/T base exchange in the promoter (p.−318), an A/G substitution in exon 1 (p.49) and a dinucleotide repeat polymorphism in exon 4 (p. 642), were associated with genetic susceptibility to multiple sclerosis (MS). We observed a significant association ( p<0.05) for homozygosity for the G 49 allele in a case-control analysis of 378 MS patients and 237 controls, and a transmission disequilibrium ( p<0.02) for the G 49 allele in 31 MS families. This was further corroborated by evidence for linkage by the affected pedigree member (APM) analysis ( p<0.0002) and a transmission distortion ( p<0.05) of the exon 4 642 polymorphism. Sequencing of the promoter, the first and second exons and the parts of the first intron revealed no further polymorphisms. Our results suggest that a dysregulation of CTLA-4-driven downregulation of T-cell activation could be involved in the pathogenesis of MS.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
