PMID- 16321988
OWN - NLM
STAT- MEDLINE
DCOM- 20060901
LR  - 20221207
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 15
IP  - 1
DP  - 2006 Jan 1
TI  - Association of the truncating splice site mutation in BTNL2 with multiple 
      sclerosis is secondary to HLA-DRB1*15.
PG  - 155-61
AB  - The major histocompatibility complex human leukocyte antigen (HLA)-DRB1*15 (DR2) 
      haplotype is strongly associated with risk of multiple sclerosis (MS). The 
      primary susceptibility has been localized to only approximately 200 kb 
      encompassing the HLA-DR and -DQ loci. Further dissection of disease association 
      with this region is demanding because of the high levels of linkage 
      disequilibrium (LD). Recently, evidence was obtained for the involvement of a 
      gene, potentially encoding an immune co-receptor, in another DR2-associated 
      inflammatory condition, sarcoidosis. The implicated gene, BTNL2, is adjacent to 
      DR and is in strong LD with HLA-DRB1. This fact, combined with a sequence 
      relationship between BTNL2 and myelin oligodendrocyte glycoprotein, an 
      autoantigen associated with MS, makes the gene an attractive candidate. To 
      determine whether BTNL2 contributes to MS, we genotyped 1136 well-characterized 
      MS families from the UK and the USA, as well as an African-American case-control 
      data set, making this among the largest genetic studies in MS. Family-based and 
      case-control association studies were performed for the BTNL2 and HLA-DRB1 loci. 
      In all family data sets, the protein-truncating allele of BTNL2, implicated in 
      sarcoidosis, was significantly over-transmitted to cases (combined data sets: 
      global P=2.4x10(-11)). Given that the protein-truncating allele of BTNL2 
      virtually always occurred with DRB1*15, an effect could only be tested in 
      DRB1*15-negative individuals or pedigrees. However, despite adequate power to 
      detect an independent association, no difference in transmission of BTNL2 alleles 
      or genotypes was observed in DRB1*15-negative individuals with MS. Conditional 
      logistic regression modeling also strongly supported the conclusion that BTNL2 
      does not confer additional disease risk. The association of BTNL2 with MS 
      observed in the African-American data set was also secondary to the primary 
      DRB1*15 association.
FAU - Traherne, James A
AU  - Traherne JA
AD  - Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Cambridge, 
      UK. jt233@cam.ac.uk
FAU - Barcellos, Lisa F
AU  - Barcellos LF
FAU - Sawcer, Stephen J
AU  - Sawcer SJ
FAU - Compston, Alastair
AU  - Compston A
FAU - Ramsay, Patricia P
AU  - Ramsay PP
FAU - Hauser, Stephen L
AU  - Hauser SL
FAU - Oksenberg, Jorge R
AU  - Oksenberg JR
FAU - Trowsdale, John
AU  - Trowsdale J
LA  - eng
GR  - 588/MSS_/Multiple Sclerosis Society/United Kingdom
GR  - G9800943/MRC_/Medical Research Council/United Kingdom
GR  - NS 46297/NS/NINDS NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20051201
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (BTNL2 protein, human)
RN  - 0 (Butyrophilins)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*15 antigen)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA Splice Sites)
SB  - IM
MH  - Black or African American/genetics
MH  - Butyrophilins
MH  - Gene Components
MH  - Genotype
MH  - HLA-DR Antigens/*genetics
MH  - HLA-DRB1 Chains
MH  - Humans
MH  - Logistic Models
MH  - Membrane Glycoproteins/*genetics
MH  - Multiple Sclerosis/*genetics
MH  - Mutation/genetics
MH  - RNA Splice Sites/genetics
MH  - United Kingdom
MH  - United States
EDAT- 2005/12/03 09:00
MHDA- 2006/09/02 09:00
CRDT- 2005/12/03 09:00
PHST- 2005/12/03 09:00 [pubmed]
PHST- 2006/09/02 09:00 [medline]
PHST- 2005/12/03 09:00 [entrez]
AID - ddi436 [pii]
AID - 10.1093/hmg/ddi436 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2006 Jan 1;15(1):155-61. doi: 10.1093/hmg/ddi436. Epub 2005 Dec 1.