PMID- 23791106
OWN - NLM
STAT- MEDLINE
DCOM- 20130916
LR  - 20211021
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 93
IP  - 1
DP  - 2013 Jul 11
TI  - Coding variants at hexa-allelic amino acid 13 of HLA-DRB1 explain independent SNP 
      associations with follicular lymphoma risk.
PG  - 167-72
LID - S0002-9297(13)00233-4 [pii]
LID - 10.1016/j.ajhg.2013.05.020 [doi]
AB  - Non-Hodgkin lymphoma represents a diverse group of blood malignancies, of which 
      follicular lymphoma (FL) is a common subtype. Previous genome-wide association 
      studies (GWASs) have identified in the human leukocyte antigen (HLA) class II 
      region multiple independent SNPs that are significantly associated with FL risk. 
      To dissect these signals and determine whether coding variants in HLA genes are 
      responsible for the associations, we conducted imputation, HLA typing, and 
      sequencing in three independent populations for a total of 689 cases and 2,446 
      controls. We identified a hexa-allelic amino acid polymorphism at position 13 of 
      the HLA-DR beta chain that showed the strongest association with FL within the 
      major histocompatibility complex (MHC) region (multiallelic p = 2.3 x 10(-)(1)(5)). Out 
      of six possible amino acids that occurred at that position within the population, 
      we classified two as high risk (Tyr and Phe), two as low risk (Ser and Arg), and 
      two as moderate risk (His and Gly). There was a 4.2-fold difference in risk (95% 
      confidence interval = 2.9-6.1) between subjects carrying two alleles encoding 
      high-risk amino acids and those carrying two alleles encoding low-risk amino 
      acids (p = 1.01 x 10(-)(1)(4)). This coding variant might explain the complex SNP 
      associations identified by GWASs and suggests a common HLA-DR antigen-driven 
      mechanism for the pathogenesis of FL and rheumatoid arthritis.
CI  - Copyright (c) 2013 The American Society of Human Genetics. Published by Elsevier 
      Inc. All rights reserved.
FAU - Foo, Jia Nee
AU  - Foo JN
AD  - Human Genetics, Genome Institute of Singapore, Agency for Science, Technology, 
      and Research, Singapore 138672, Singapore.
FAU - Smedby, Karin E
AU  - Smedby KE
FAU - Akers, Nicholas K
AU  - Akers NK
FAU - Berglund, Mattias
AU  - Berglund M
FAU - Irwan, Ishak D
AU  - Irwan ID
FAU - Jia, Xiaoming
AU  - Jia X
FAU - Li, Yi
AU  - Li Y
FAU - Conde, Lucia
AU  - Conde L
FAU - Darabi, Hatef
AU  - Darabi H
FAU - Bracci, Paige M
AU  - Bracci PM
FAU - Melbye, Mads
AU  - Melbye M
FAU - Adami, Hans-Olov
AU  - Adami HO
FAU - Glimelius, Bengt
AU  - Glimelius B
FAU - Khor, Chiea Chuen
AU  - Khor CC
FAU - Hjalgrim, Henrik
AU  - Hjalgrim H
FAU - Padyukov, Leonid
AU  - Padyukov L
FAU - Humphreys, Keith
AU  - Humphreys K
FAU - Enblad, Gunilla
AU  - Enblad G
FAU - Skibola, Christine F
AU  - Skibola CF
FAU - de Bakker, Paul I W
AU  - de Bakker PI
FAU - Liu, Jianjun
AU  - Liu J
LA  - eng
GR  - CA89745/CA/NCI NIH HHS/United States
GR  - CA122663/CA/NCI NIH HHS/United States
GR  - CA104682/CA/NCI NIH HHS/United States
GR  - R01 CA154643/CA/NCI NIH HHS/United States
GR  - R01 CA104682/CA/NCI NIH HHS/United States
GR  - R01 CA045614/CA/NCI NIH HHS/United States
GR  - R03 CA089745/CA/NCI NIH HHS/United States
GR  - CA069269-01/CA/NCI NIH HHS/United States
GR  - R01 CA122663/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130620
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Amino Acids)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - *Alleles
MH  - Amino Acids/genetics/*metabolism
MH  - Case-Control Studies
MH  - Confidence Intervals
MH  - Gene Frequency
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Genetics, Population/methods
MH  - HLA-DRB1 Chains/*genetics/metabolism
MH  - Haplotypes
MH  - Histocompatibility Testing
MH  - Humans
MH  - Lymphoma, Follicular/*genetics/metabolism
MH  - Open Reading Frames
MH  - *Polymorphism, Single Nucleotide
MH  - Risk Factors
PMC - PMC3710749
EDAT- 2013/06/25 06:00
MHDA- 2013/09/17 06:00
PMCR- 2014/01/11
CRDT- 2013/06/25 06:00
PHST- 2013/04/08 00:00 [received]
PHST- 2013/05/21 00:00 [revised]
PHST- 2013/05/23 00:00 [accepted]
PHST- 2013/06/25 06:00 [entrez]
PHST- 2013/06/25 06:00 [pubmed]
PHST- 2013/09/17 06:00 [medline]
PHST- 2014/01/11 00:00 [pmc-release]
AID - S0002-9297(13)00233-4 [pii]
AID - AJHG1448 [pii]
AID - 10.1016/j.ajhg.2013.05.020 [doi]
PST - ppublish
SO  - Am J Hum Genet. 2013 Jul 11;93(1):167-72. doi: 10.1016/j.ajhg.2013.05.020. Epub 
      2013 Jun 20.