PMID- 12557126
OWN - NLM
STAT- MEDLINE
DCOM- 20030424
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Linking)
VI  - 72
IP  - 3
DP  - 2003 Mar
TI  - HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on 
      disease course.
PG  - 710-6
AB  - Models of disease susceptibility in multiple sclerosis (MS) often assume a 
      dominant action for the HLA-DRB1*1501 allele and its associated haplotype 
      (DRB1*1501-DQB1*0602 or DR2). A robust and phenotypically well-characterized MS 
      data set was used to explore this model in more detail. A dose effect of HLA-DR2 
      haplotypes on MS susceptibility was revealed. This observation suggests that, in 
      addition to the role of HLA-DR2 in MS, two copies of a susceptibility haplotype 
      further increase disease risk. Second, we report that DR2 haplotypes modify 
      disease expression. There is a paucity of benign MS and an increase of severe MS 
      in individuals homozygous for DR2. Concepts of the molecular mechanisms that 
      underlie linkage and association of the human leukocyte antigen (HLA) region to 
      MS need to be revised to accommodate these data.
FAU - Barcellos, L F
AU  - Barcellos LF
AD  - Department of Neurology, University of California at San Francisco, San 
      Francisco, CA, USA.
FAU - Oksenberg, J R
AU  - Oksenberg JR
FAU - Begovich, A B
AU  - Begovich AB
FAU - Martin, E R
AU  - Martin ER
FAU - Schmidt, S
AU  - Schmidt S
FAU - Vittinghoff, E
AU  - Vittinghoff E
FAU - Goodin, D S
AU  - Goodin DS
FAU - Pelletier, D
AU  - Pelletier D
FAU - Lincoln, R R
AU  - Lincoln RR
FAU - Bucher, P
AU  - Bucher P
FAU - Swerdlin, A
AU  - Swerdlin A
FAU - Pericak-Vance, M A
AU  - Pericak-Vance MA
FAU - Haines, J L
AU  - Haines JL
FAU - Hauser, S L
AU  - Hauser SL
CN  - Multiple Sclerosis Genetics Group
LA  - eng
SI  - OMIM/126200
SI  - OMIM/142857
SI  - OMIM/604305
GR  - R01 AG020135/AG/NIA NIH HHS/United States
GR  - NS26799/NS/NINDS NIH HHS/United States
GR  - AG-20135-01/AG/NIA NIH HHS/United States
GR  - R01 NS032830/NS/NINDS NIH HHS/United States
GR  - R01 NS026799/NS/NINDS NIH HHS/United States
GR  - NS32830/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030128
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DR2 Antigen)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Disease Progression
MH  - Female
MH  - Gene Dosage
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genotype
MH  - HLA-DR Antigens/genetics
MH  - HLA-DR2 Antigen/*genetics
MH  - HLA-DRB1 Chains
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Multiple Sclerosis/*genetics/immunology/physiopathology
MH  - Phenotype
MH  - Risk Assessment
PMC - PMC1180245
EDAT- 2003/01/31 04:00
MHDA- 2003/04/25 05:00
PMCR- 2003/09/01
CRDT- 2003/01/31 04:00
PHST- 2002/09/04 00:00 [received]
PHST- 2002/11/25 00:00 [accepted]
PHST- 2003/01/31 04:00 [pubmed]
PHST- 2003/04/25 05:00 [medline]
PHST- 2003/01/31 04:00 [entrez]
PHST- 2003/09/01 00:00 [pmc-release]
AID - S0002-9297(07)60586-2 [pii]
AID - 024448 [pii]
AID - 10.1086/367781 [doi]
PST - ppublish
SO  - Am J Hum Genet. 2003 Mar;72(3):710-6. doi: 10.1086/367781. Epub 2003 Jan 28.