These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: A NOTCH4 association with multiple sclerosis is secondary to HLA-DR*1501.
    Author: Duvefelt K, Anderson M, Fogdell-Hahn A, Hillert J.
    Journal: Tissue Antigens; 2004 Jan; 63(1):13-20. PubMed ID: 14651518.
    Abstract:
    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) with supposedly autoimmune features known to be associated with a specific HLA DR-DQ haplotype (DR15, DQ6, or HLDRB1*1501,DRB5*0101,DQA1*0102,DQB1*0602). We have previously reported that the associated haplotype extends to HLA-B and described an independent association with HLA-A alleles in MS. Owing to a complex situation with extensive linkage disequilibria, it is still unclear whether classical HLA genes are responsible or whether associations may be due to other genes in this region. Here, we analyzed an association in MS with the NOTCH4 and TNFalpha (tumor necrosis factor-alpha) genes, located between the HLA-DRB1 gene and the HLA-A gene. For NOTCH4, located 0.4 Mb telomeric to HLA-DRB1, an SNP at position -25 and a trinucleotide repeat were investigated in 181 MS patients, and 180 controls also typed P = 0.027 for HLA-DRB and HLA-A. A modest association was observed (OR = 3.44) with the C-25 allele. However, two-locus analysis revealed that this association was secondary to the classical association with HLA-DRB1. For TNF, located 0.7 Mb telomeric of NOTCH4, SNPs at positions -308 and -238 were studied in the same dataset. We found no association between these TNFalpha gene polymorphisms and MS in this dataset, although there was linkage disequilibrium (LD) between DRB1 and TNF and between HLA-A and TNF. We conclude that alleles of the NOTCH4 and TNFalpha genes are unlikely to be of importance for the susceptibility to MS, although specific alleles of these genes are often carried on the same haplotype as DR15, DQ6.
    [Abstract] [Full Text] [Related] [New Search]