PMID- 22170232
OWN - NLM
STAT- MEDLINE
DCOM- 20120820
LR  - 20240404
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Print)
IS  - 1466-4879 (Linking)
VI  - 13
IP  - 3
DP  - 2012 Apr
TI  - Amino acid position 11 of HLA-DRbeta1 is a major determinant of chromosome 6p 
      association with ulcerative colitis.
PG  - 245-52
LID - 10.1038/gene.2011.79 [doi]
AB  - The major histocompatibility complex (MHC) on chromosome 6p is an established 
      risk locus for ulcerative colitis (UC) and Crohn's disease (CD). We aimed to 
      better define MHC association signals in UC and CD by combining data from dense 
      single-nucleotide polymorphism (SNP) genotyping and from imputation of classical 
      human leukocyte antigen (HLA) types, their constituent SNPs and corresponding 
      amino acids in 562 UC, 611 CD and 1428 control subjects. Univariate and 
      multivariate association analyses were performed, controlling for ancestry. In 
      univariate analyses, absence of the rs9269955 C allele was strongly associated 
      with risk for UC (P = 2.67 x 10(-13)). rs9269955 is a SNP in the codon for amino 
      acid position 11 of HLA-DRbeta1, located in the P6 pocket of the HLA-DR antigen 
      binding cleft. This amino acid position was also the most significantly 
      UC-associated amino acid in omnibus tests (P = 2.68 x 10(-13)). Multivariate 
      modeling identified rs9269955-C and 13 other variants in best predicting UC vs 
      control status. In contrast, there was only suggestive association evidence 
      between the MHC and CD. Taken together, these data demonstrate that variation at 
      HLA-DRbeta1, amino acid 11 in the P6 pocket of the HLA-DR complex antigen binding 
      cleft is a major determinant of chromosome 6p association with UC.
FAU - Achkar, J-P
AU  - Achkar JP
AD  - Department of Gastroenterology and Hepatology, Digestive Disease Institute, 
      Cleveland Clinic, Cleveland, OH, USA.
FAU - Klei, L
AU  - Klei L
FAU - de Bakker, P I W
AU  - de Bakker PI
FAU - Bellone, G
AU  - Bellone G
FAU - Rebert, N
AU  - Rebert N
FAU - Scott, R
AU  - Scott R
FAU - Lu, Y
AU  - Lu Y
FAU - Regueiro, M
AU  - Regueiro M
FAU - Brzezinski, A
AU  - Brzezinski A
FAU - Kamboh, M I
AU  - Kamboh MI
FAU - Fiocchi, C
AU  - Fiocchi C
FAU - Devlin, B
AU  - Devlin B
FAU - Trucco, M
AU  - Trucco M
FAU - Ringquist, S
AU  - Ringquist S
FAU - Roeder, K
AU  - Roeder K
FAU - Duerr, R H
AU  - Duerr RH
LA  - eng
GR  - DK076025/DK/NIDDK NIH HHS/United States
GR  - DK068112/DK/NIDDK NIH HHS/United States
GR  - U01 DK062420-05/DK/NIDDK NIH HHS/United States
GR  - R01 MH057881/MH/NIMH NIH HHS/United States
GR  - U01 DK062420-01/DK/NIDDK NIH HHS/United States
GR  - AG030653/AG/NIA NIH HHS/United States
GR  - R01 DK076025/DK/NIDDK NIH HHS/United States
GR  - DK062420/DK/NIDDK NIH HHS/United States
GR  - R01 AG030653/AG/NIA NIH HHS/United States
GR  - K23 DK068112/DK/NIDDK NIH HHS/United States
GR  - U01 DK062420-08/DK/NIDDK NIH HHS/United States
GR  - U01 DK062420-08S1/DK/NIDDK NIH HHS/United States
GR  - U01 DK062420-04/DK/NIDDK NIH HHS/United States
GR  - R01 DK076025-02/DK/NIDDK NIH HHS/United States
GR  - R37 MH057881/MH/NIMH NIH HHS/United States
GR  - U01 DK062420-09/DK/NIDDK NIH HHS/United States
GR  - U01 DK062420-02/DK/NIDDK NIH HHS/United States
GR  - U01 DK062420-07/DK/NIDDK NIH HHS/United States
GR  - MH057881/MH/NIMH NIH HHS/United States
GR  - U01 DK062420-06/DK/NIDDK NIH HHS/United States
GR  - U01 DK062420-03/DK/NIDDK NIH HHS/United States
GR  - U01 DK062420-10/DK/NIDDK NIH HHS/United States
GR  - U01 DK062420/DK/NIDDK NIH HHS/United States
GR  - R01 DK076025-01A1/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20111215
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (HLA-DR beta-Chains)
SB  - IM
MH  - Alleles
MH  - Amino Acid Substitution
MH  - *Chromosomes, Human, Pair 6
MH  - Colitis, Ulcerative/*genetics
MH  - Crohn Disease/genetics
MH  - Gene Frequency
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - HLA-DR beta-Chains/*genetics
MH  - Humans
MH  - Polymorphism, Single Nucleotide
PMC - PMC3341846
MID - NIHMS352873
COIS- Conflict of interests: The authors declare no conflict of interest.
EDAT- 2011/12/16 06:00
MHDA- 2012/08/21 06:00
PMCR- 2012/10/01
CRDT- 2011/12/16 06:00
PHST- 2011/12/16 06:00 [entrez]
PHST- 2011/12/16 06:00 [pubmed]
PHST- 2012/08/21 06:00 [medline]
PHST- 2012/10/01 00:00 [pmc-release]
AID - gene201179 [pii]
AID - 10.1038/gene.2011.79 [doi]
PST - ppublish
SO  - Genes Immun. 2012 Apr;13(3):245-52. doi: 10.1038/gene.2011.79. Epub 2011 Dec 15.