PMID- 11175794
OWN - NLM
STAT- MEDLINE
DCOM- 20010315
LR  - 20081121
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 27
IP  - 2
DP  - 2001 Feb
TI  - Linkage disequilibrium of a type 1 diabetes susceptibility locus with a 
      regulatory IL12B allele.
PG  - 218-21
AB  - Type 1 diabetes (T1D; or insulin-dependent diabetes mellitus, IDDM) is an 
      autoimmune disease with both genetic and environmental components. In addition to 
      the human leukocyte antigen (HLA) complex, the single major genetic contributor 
      of susceptibility, an unknown number of other unidentified genes are required to 
      mediate disease. Although many loci conferring susceptibility to T1D have been 
      mapped, their identification has proven problematic due to the complex nature of 
      this disease. Our strategy for finding T1D susceptibility genes has been to test 
      for human homologues of loci implicated in diabetes-prone NOD (non-obese 
      diabetic) mice, together with application of biologically relevant stratification 
      methods. We report here a new susceptibility locus, IDDM18, located near the 
      interleukin-12 (IL-12)p40 gene, IL12B. Significant bias in transmission of IL12B 
      alleles was observed in affected sibpairs and was confirmed in an independent 
      cohort of simplex families. A single base change in the 3' UTR showed strong 
      linkage disequilibrium with the T1D susceptibility locus. The IL12B 3' UTR 
      alleles showed different levels of expression in cell lines. Variation in 
      IL-12p40 production may influence T-cell responses crucial for either mediating 
      or protecting against this and other autoimmune diseases.
FAU - Morahan, G
AU  - Morahan G
AD  - The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne 
      Hospital, Victoria, Australia. morahan@wehi.edu.au
FAU - Huang, D
AU  - Huang D
FAU - Ymer, S I
AU  - Ymer SI
FAU - Cancilla, M R
AU  - Cancilla MR
FAU - Stephen, K
AU  - Stephen K
FAU - Dabadghao, P
AU  - Dabadghao P
FAU - Werther, G
AU  - Werther G
FAU - Tait, B D
AU  - Tait BD
FAU - Harrison, L C
AU  - Harrison LC
FAU - Colman, P G
AU  - Colman PG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (3' Untranslated Regions)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
EIN - Nat Genet 2001 Mar;27(3):346
CIN - Nat Genet. 2001 Feb;27(2):131-2. PMID: 11175771
MH  - 3' Untranslated Regions
MH  - Alleles
MH  - Diabetes Mellitus, Type 1/*genetics
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Interleukin-12/*genetics
MH  - Introns
MH  - *Linkage Disequilibrium
MH  - Polymorphism, Genetic
MH  - Promoter Regions, Genetic
EDAT- 2001/02/15 11:00
MHDA- 2001/03/17 10:01
CRDT- 2001/02/15 11:00
PHST- 2001/02/15 11:00 [pubmed]
PHST- 2001/03/17 10:01 [medline]
PHST- 2001/02/15 11:00 [entrez]
AID - 10.1038/84872 [doi]
PST - ppublish
SO  - Nat Genet. 2001 Feb;27(2):218-21. doi: 10.1038/84872.