PMID- 14679086
OWN - NLM
STAT- MEDLINE
DCOM- 20040116
LR  - 20190616
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 1005
DP  - 2003 Nov
TI  - Mutation scan of a type 1 diabetes candidate gene: the human interleukin-18 
      binding protein gene.
PG  - 332-9
AB  - Type 1 (insulin-dependent) diabetes, T1DM, is the result of an immune-mediated 
      destruction of the pancreatic beta cells dependent mainly on T helper cells and 
      macrophages. Interleukin-18 (IL-18) is a proinflammatory cytokine produced mainly 
      by macrophages. IL-18 is capable of inducing T lymphocyte synthesis of IFNgamma, 
      thereby skewing the T helper response toward a T helper type 1 (Th1) profile. 
      IL-18 binding protein (IL18BP) neutralizes IL-18 and leads to a reduced Th1 
      response. Polymorphisms in IL18BP may affect the activity of IL-18 and the 
      magnitude of the Th1 response and may play a role in the pathogenesis of T1DM. 
      The aim of the study was therefore to identify polymorphisms in IL18BP and to 
      test these for association with T1DM. We evaluated the human IL18BP gene on 
      chromosome 11q13 as a candidate susceptibility gene for T1DM and scanned the 
      entire IL18BP (promoter, exons 1-6, and 3'UTR) for polymorphisms using 
      single-strand conformational polymorphism analysis and direct sequencing. We 
      identified a total of 11 polymorphisms, all having allele frequencies ranging 
      between 0.05 and 0.10. Four were in the 5'UTR: -257G-->T, -78C-->T, -65G-->A, and 
      -59A-->G. Three were in intron 3: IVS3+140A-->C, IVS4-147G-->T, and IVS4-59G-->T. 
      The last four, 38*A-->T, 48*T-->A, 388*C-->G, and 440*_441*insG, were in the 
      3'UTR of IL18BP. However, none of these were frequent enough to permit 
      association studies in T1DM and we conclude that IL18BP does not contribute to 
      the overall genetic susceptibility to type 1 diabetes.
FAU - Nolsoe, Runa L
AU  - Nolsoe RL
AD  - Steno Diabetes Center, Gentofte, Denmark.
FAU - Pociot, Flemming
AU  - Pociot F
FAU - Novick, Daniela
AU  - Novick D
FAU - Rubinstein, Menachem
AU  - Rubinstein M
FAU - Kim, Soo-Hyun
AU  - Kim SH
FAU - Dinarello, Charles A
AU  - Dinarello CA
FAU - Mandrup-Poulsen, Thomas
AU  - Mandrup-Poulsen T
LA  - eng
GR  - AI-15614/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (DNA Primers)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (interleukin-18 binding protein)
SB  - IM
MH  - Base Sequence
MH  - Chromosomes, Human, Pair 11
MH  - DNA Primers
MH  - Diabetes Mellitus, Type 1/*genetics
MH  - Glycoproteins/*genetics
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - *Mutation
EDAT- 2003/12/18 05:00
MHDA- 2004/01/17 05:00
CRDT- 2003/12/18 05:00
PHST- 2003/12/18 05:00 [pubmed]
PHST- 2004/01/17 05:00 [medline]
PHST- 2003/12/18 05:00 [entrez]
AID - 10.1196/annals.1288.053 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2003 Nov;1005:332-9. doi: 10.1196/annals.1288.053.