PMID- 10626741
OWN - NLM
STAT- MEDLINE
DCOM- 20000420
LR  - 20201208
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 60
IP  - 12
DP  - 1999 Dec
TI  - Susceptibility to multiple sclerosis mediated by HLA-DRB1 is influenced by a 
      second gene telomeric of the TNF cluster.
PG  - 1266-73
AB  - Susceptibility to multiple sclerosis (MS) is clearly associated with human 
      leukocyte antigen (HLA)-DRB1*1501, but some studies show associations with HLA-B7 
      and -B18. These are often co-expressed with DRB1*1501 in the ancestral haplotypes 
      (AH) denoted 7.1 (HLA-A3, B7, tumor necrosis factor [TNF]a11b4, DRB1*1501) and 
      18.1 (HLA-A25, B18, TNFa10b4, DRB 1*1501). Here we present a systematic study of 
      218 patients and 274 controls typed at all standard class II and TNF 
      microsatellite loci, and a novel non-synonymous polymorphism in the central major 
      histocompatibility complex gene, inhibitor of kappa B-like protein (IKBL). The C 
      allele at IKBL+738 is only found on the 7.1 haplotype. HLA-DRB1*1501 was 
      associated with disease, as expected. When subjects expressing DRB 1*501 were 
      analyzed separately, TNFa11b4 and IKBL+738C were less common in the patients and, 
      hence, mark an allele that mediates resistance which lies telomeric of IKBL. 
      TNFa10b4 and TNFa1b5 were more common in DRB1*1501 patients than in controls. 
      These alleles have been associated with the 18.1 and 18.2 AH, respectively. Since 
      no component of these haplotypes was an independent risk factor in this study, it 
      appears likely that a gene linked to TNFa10b4 and TNFa1b5 modifies the effect of 
      the susceptibility locus marked by HLA-DRB1*1501. Potential candidate genes 
      telomeric of the TNF cluster are discussed.
FAU - Allcock, R J
AU  - Allcock RJ
AD  - Department of Biochemistry, University of Western Australia, Nedlands. 
      rallock@dci.uwa.edu.au
FAU - de la Concha, E G
AU  - de la Concha EG
FAU - Fernandez-Arquero, M
AU  - Fernandez-Arquero M
FAU - Vigil, P
AU  - Vigil P
FAU - Conejero, L
AU  - Conejero L
FAU - Arroyo, R
AU  - Arroyo R
FAU - Price, P
AU  - Price P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (NFKBIL1 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Adult
MH  - Alleles
MH  - Cohort Studies
MH  - Female
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - HLA-DR Antigens/*genetics
MH  - HLA-DRB1 Chains
MH  - Histocompatibility Antigens Class II/genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Multigene Family
MH  - Multiple Sclerosis/*genetics/immunology
MH  - *Telomere
MH  - Tumor Necrosis Factor-alpha/*genetics
EDAT- 2000/01/08 09:00
MHDA- 2000/04/25 09:00
CRDT- 2000/01/08 09:00
PHST- 2000/01/08 09:00 [pubmed]
PHST- 2000/04/25 09:00 [medline]
PHST- 2000/01/08 09:00 [entrez]
AID - S0198-8859(99)00127-5 [pii]
AID - 10.1016/s0198-8859(99)00127-5 [doi]
PST - ppublish
SO  - Hum Immunol. 1999 Dec;60(12):1266-73. doi: 10.1016/s0198-8859(99)00127-5.