PMID- 21631897
OWN - NLM
STAT- MEDLINE
DCOM- 20120125
LR  - 20211020
IS  - 1753-0407 (Electronic)
IS  - 1753-0393 (Print)
IS  - 1753-0407 (Linking)
VI  - 3
IP  - 3
DP  - 2011 Sep
TI  - Replication and further characterization of a Type 1 diabetes-associated locus at 
      the telomeric end of the major histocompatibility complex.
PG  - 238-47
LID - 10.1111/j.1753-0407.2011.00131.x [doi]
AB  - BACKGROUND: We recently reported an association between Type 1 diabetes and the 
      telomeric major histocompatibility complex (MHC) single nucleotide polymorphism 
      (SNP) rs1233478. As further families have been analyzed in the Type 1 Diabetes 
      Genetics Consortium (T1DGC), we tested replication of the association and, with 
      more data, analyzed haplotypic associations. METHODS: An additional 2717 case and 
      1315 control chromosomes have been analyzed from the T1DGC, with human leukocyte 
      antigen (HLA) typing and data for 2837 SNPs across the MHC region. RESULTS: We 
      confirmed the association of rs1233478 (new data only: P=2.2E-5, OR=1.4). We also 
      found two additional SNPs nearby that were significantly associated with Type 1 
      diabetes (new data only rs3131020: P=8.3E-9, OR=0.65; rs1592410: P=2.2E-8, 
      OR=1.5). For studies of Type 1 diabetes in the MHC region, it is critical to 
      account for linkage disequilibrium with the HLA genes. Logistic regression 
      analysis of these new data indicated that the effects of rs3131020 and rs1592410 
      on Type 1 diabetes risk are independent of HLA alleles (rs3131020: P=2.3E-3, 
      OR=0.73; rs1592410: P=2.1E-3, OR=1.4). Haplotypes of 12 SNPs (including the three 
      highly significant SNPs) stratify diabetes risk (high risk, protective, and 
      neutral), with high-risk haplotypes limited to approximately 20,000 bp in length. 
      The 20,000-bp region is telomeric of the UBD gene and contains LOC729653, a 
      hypothetical gene. CONCLUSIONS: We believe that polymorphisms of the telomeric 
      MHC locus LOC729653 may confer risk for Type 1 diabetes.
CI  - (c) 2011 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and 
      Blackwell Publishing Asia Pty Ltd.
FAU - Baschal, Erin E
AU  - Baschal EE
AD  - Barbara Davis Center for Childhood Diabetes, University of Colorado-Denver, 1775 
      Aurora Ct., Aurora, CO 80045, USA.
FAU - Sarkar, Suparna A
AU  - Sarkar SA
FAU - Boyle, Theresa A
AU  - Boyle TA
FAU - Siebert, Janet C
AU  - Siebert JC
FAU - Jasinski, Jean M
AU  - Jasinski JM
FAU - Grabek, Katharine R
AU  - Grabek KR
FAU - Armstrong, Taylor K
AU  - Armstrong TK
FAU - Babu, Sunanda R
AU  - Babu SR
FAU - Fain, Pamela R
AU  - Fain PR
FAU - Steck, Andrea K
AU  - Steck AK
FAU - Rewers, Marian J
AU  - Rewers MJ
FAU - Eisenbarth, George S
AU  - Eisenbarth GS
LA  - eng
GR  - R01 DK32083/DK/NIDDK NIH HHS/United States
GR  - P30 DK57516/DK/NIDDK NIH HHS/United States
GR  - AI050864/AI/NIAID NIH HHS/United States
GR  - R37 DK32493/DK/NIDDK NIH HHS/United States
GR  - R01 DK032083-28/DK/NIDDK NIH HHS/United States
GR  - R01 DK032493/DK/NIDDK NIH HHS/United States
GR  - K01 DK080193/DK/NIDDK NIH HHS/United States
GR  - R01 DK032083/DK/NIDDK NIH HHS/United States
GR  - AI15416/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Australia
TA  - J Diabetes
JT  - Journal of diabetes
JID - 101504326
RN  - 0 (HLA Antigens)
RN  - 0 (UBD protein, human)
RN  - 0 (Ubiquitins)
SB  - IM
MH  - Base Sequence
MH  - DNA Replication
MH  - Diabetes Mellitus, Type 1/*genetics
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Frequency
MH  - Genetic Loci/genetics
MH  - Genotype
MH  - HLA Antigens/genetics
MH  - *Haplotypes
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Logistic Models
MH  - Major Histocompatibility Complex/*genetics
MH  - Male
MH  - Molecular Sequence Data
MH  - *Polymorphism, Single Nucleotide
MH  - Sequence Analysis, DNA
MH  - Telomere/genetics
MH  - Ubiquitins/genetics
PMC - PMC3610173
MID - NIHMS293110
EDAT- 2011/06/03 06:00
MHDA- 2012/01/26 06:00
PMCR- 2013/03/28
CRDT- 2011/06/03 06:00
PHST- 2011/06/03 06:00 [entrez]
PHST- 2011/06/03 06:00 [pubmed]
PHST- 2012/01/26 06:00 [medline]
PHST- 2013/03/28 00:00 [pmc-release]
AID - 10.1111/j.1753-0407.2011.00131.x [doi]
PST - ppublish
SO  - J Diabetes. 2011 Sep;3(3):238-47. doi: 10.1111/j.1753-0407.2011.00131.x.