PMID- 12196647
OWN - NLM
STAT- MEDLINE
DCOM- 20020920
LR  - 20190514
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 59
IP  - 4
DP  - 2002 Aug 27
TI  - Evidence for additional genetic risk indicators of relapse-onset MS within the 
      HLA region.
PG  - 549-55
AB  - BACKGROUND: Human leukocyte antigen (HLA)-DR2 carriership is associated with an 
      increased risk for MS. Genome searches using microsatellite markers have 
      consistently shown that additional genetic factors contribute to susceptibility 
      for MS. OBJECTIVE: To identify loci within the HLA region that predispose to 
      relapse-onset MS independently of HLA-DR2. METHOD: A case-control study involving 
      159 patients with definite relapse-onset MS and 273 control subjects was 
      conducted. Six highly polymorphic microsatellite markers encoded within the HLA-C 
      to DR region, that is, D6S1014, D6S273, TNFa, MIB, C1_2_5, and C1_3_2, three 
      single-nucleotide tumor necrosis factor (TNF) promoter gene polymorphisms at 
      positions -238, -308, and -376, and HLA-DR2 carriership were typed. RESULTS: 
      These data confirmed the well-known association between the HLA-DR2 haplotype and 
      relapse-onset MS, yielding an odds ratio (OR) of 3.6 (95% CI: 2.4 to 5.4; p < 
      0.0001). Multivariate analyses revealed that C1_3_2*354 was also associated with 
      an increased risk for developing relapse-onset MS independently of HLA-DR2 (OR: 
      2.0; 95% CI: 1.2 to 3.1; p = 0.004). This allele is encoded within an ancestral 
      haplotype that is highly linked to HLA-DR3. The joint effect of this ancestral 
      haplotype and HLA-DR2 resulted in an OR of 8.7 (95% CI: 2.7 to 29; p < 0.0001) to 
      develop relapse-onset MS. In addition, a protective risk factor was found: 
      carriers of TNFa*107 had a 0.5-fold lower risk to develop relapse-onset MS (95% 
      CI: 0.3 to 0.9; p = 0.026). CONCLUSION: Within the HLA region, other loci besides 
      HLA-DR2 haplotype modulate susceptibility for relapse-onset MS.
FAU - de Jong, B A
AU  - de Jong BA
AD  - Department of Clinical Epidemiology, LUMC, Leiden, The Netherlands.
FAU - Huizinga, T W J
AU  - Huizinga TW
FAU - Zanelli, E
AU  - Zanelli E
FAU - Giphart, M J
AU  - Giphart MJ
FAU - Bollen, E L E M
AU  - Bollen EL
FAU - Uitdehaag, B M J
AU  - Uitdehaag BM
FAU - Polman, C H
AU  - Polman CH
FAU - Westendorp, R G J
AU  - Westendorp RG
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (HLA-DR2 Antigen)
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Case-Control Studies
MH  - Female
MH  - Gene Dosage
MH  - Genetic Linkage
MH  - *Genetic Predisposition to Disease
MH  - Genetic Testing
MH  - HLA-DR2 Antigen/*genetics
MH  - HLA-DR3 Antigen/genetics
MH  - Haplotypes
MH  - Heterozygote
MH  - Histocompatibility Testing
MH  - Humans
MH  - Male
MH  - Microsatellite Repeats/genetics
MH  - Middle Aged
MH  - Multiple Sclerosis, Relapsing-Remitting/epidemiology/*genetics
MH  - Multivariate Analysis
MH  - Netherlands/epidemiology
MH  - Odds Ratio
MH  - Promoter Regions, Genetic/genetics
MH  - Risk Assessment
MH  - Risk Factors
MH  - Tumor Necrosis Factor-alpha/genetics
EDAT- 2002/08/28 10:00
MHDA- 2002/09/21 10:01
CRDT- 2002/08/28 10:00
PHST- 2002/08/28 10:00 [pubmed]
PHST- 2002/09/21 10:01 [medline]
PHST- 2002/08/28 10:00 [entrez]
AID - 10.1212/wnl.59.4.549 [doi]
PST - ppublish
SO  - Neurology. 2002 Aug 27;59(4):549-55. doi: 10.1212/wnl.59.4.549.