PMID- 17257319
OWN - NLM
STAT- MEDLINE
DCOM- 20070516
LR  - 20070129
IS  - 0001-2815 (Print)
IS  - 0001-2815 (Linking)
VI  - 69
IP  - 2
DP  - 2007 Feb
TI  - Primary sclerosing cholangitis is associated with extended HLA-DR3 and HLA-DR6 
      haplotypes.
PG  - 161-9
AB  - Primary sclerosing cholangitis (PSC) is associated with the human leukocyte 
      antigen (HLA)-DRB1*0301-DQA1*0501-DQB1*0201 (DR3) and 
      HLA-DRB1*1301-DQA1*0103-DQB1*0603 (DR6) haplotypes. Recently, the extended HLA 
      class I region has been found to harbour genes that modulate or confer 
      susceptibility independently of the HLA class II genes in several immune-mediated 
      diseases. The aim of the present study was to evaluate the influence of genes in 
      the extended HLA class I region on susceptibility to PSC. Seven microsatellite 
      markers (MIB, D6S265, D6S2222, D6S464, D6S2223, D6S2225 and D6S2239) were 
      analysed together with HLA class II alleles in 219 Norwegian patients with PSC 
      and 282 random controls. To control for associations because of linkage 
      disequilibrium (LD), 142 HLA-DR3 homozygous and 187 DR6-positive controls were 
      included. The unstratified analysis showed significant associations with the 
      alleles MIB*349 [odds ratio (OR) = 3.0, corrected P value (P(c)) = 3 x 10(-12)], 
      D6S265*122 (OR = 1.7, P(c)= 0.004), D6S464*209 (OR = 1.8, P(c)= 0.03) and 
      D6S2225*147 (OR = 2.7, P(c)= 4 x 10(-6)), which were mainly secondary to the DR3 
      association. When stratifying for DR6, an association with the D6S265*122 allele 
      was still observed (OR = 3.7, P(c)= 0.0004). In the presence of the D6S265*122 
      allele, the risk to develop PSC conferred by DR6 was increased four times 
      compared with the risk conferred by DR6 alone. In addition, a novel negative 
      association of PSC with DR11 was observed (OR = 0.21, P(c)= 2 x 10(-4)). In 
      conclusion, our study shows that a gene in LD with D6S265 contributes to 
      susceptibility to develop PSC in individuals carrying DR6. Moreover, we found 
      that the PSC-associated DR3 haplotype extends more telomeric than that previously 
      reported. We also report a possible protective effect of DR11 on development of 
      PSC.
FAU - Wiencke, K
AU  - Wiencke K
AD  - Medical Department, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. 
      kristine.wiencke@medisin.uio.no
FAU - Karlsen, T H
AU  - Karlsen TH
FAU - Boberg, K M
AU  - Boberg KM
FAU - Thorsby, E
AU  - Thorsby E
FAU - Schrumpf, E
AU  - Schrumpf E
FAU - Lie, B A
AU  - Lie BA
FAU - Spurkland, A
AU  - Spurkland A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Tissue Antigens
JT  - Tissue antigens
JID - 0331072
RN  - 0 (Genetic Markers)
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (HLA-DR6 Antigen)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - Case-Control Studies
MH  - Child
MH  - Cholangitis, Sclerosing/genetics/*immunology
MH  - Chromosomes, Human, Pair 6/genetics
MH  - Genetic Markers
MH  - Genetic Predisposition to Disease
MH  - HLA-DR3 Antigen/*genetics
MH  - HLA-DR6 Antigen/*genetics
MH  - Haplotypes
MH  - Histocompatibility Antigens Class I/*genetics
MH  - Histocompatibility Antigens Class II/genetics
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Microsatellite Repeats
MH  - Middle Aged
EDAT- 2007/01/30 09:00
MHDA- 2007/05/17 09:00
CRDT- 2007/01/30 09:00
PHST- 2007/01/30 09:00 [pubmed]
PHST- 2007/05/17 09:00 [medline]
PHST- 2007/01/30 09:00 [entrez]
AID - TAN738 [pii]
AID - 10.1111/j.1399-0039.2006.00738.x [doi]
PST - ppublish
SO  - Tissue Antigens. 2007 Feb;69(2):161-9. doi: 10.1111/j.1399-0039.2006.00738.x.