PMID- 14709415
OWN - NLM
STAT- MEDLINE
DCOM- 20041104
LR  - 20191108
IS  - 0896-8411 (Print)
IS  - 0896-8411 (Linking)
VI  - 22
IP  - 1
DP  - 2004 Feb
TI  - Association between IL-18 gene promoter polymorphisms and CTLA-4 gene 49A/G 
      polymorphism in Japanese patients with type 1 diabetes.
PG  - 73-8
AB  - Interleukin-18 (IL-18) is a potent proinflammatory cytokine which is strongly 
      associated with the development of diabetes in NOD mice. To test the putative 
      involvement of IL-18 gene polymorphism in predisposition to human type 1 
      diabetes, the SNPs at position -607 (C/A) and -137 (G/C) in the promoter region 
      of IL-18 gene were analyzed by sequence-specific PCR in 116 patients with type 1 
      diabetes and 114 normal controls. A linkage disequilibrium found only three of 
      the four possible haplotypes defined by these SNPs. The distribution of the IL-18 
      gene genotypes at position -607 was significantly different between patients with 
      type 1 diabetes and normal controls (P=0.023). Furthermore, there was a 
      significant increase in haplotype 1 (-607C/-137G) in the patients compared with 
      controls (P=0.006). The association study of the susceptible CTLA-4 genotype (GG 
      at nucleotide position 49 in exon 1) or HLA-DR4-DQB1*0401 and type 1 diabetes 
      showed that the predisposing IL-18 gene haplotype modulates the risk on CTLA-4 GG 
      genotype, but not on HLA-DR4-DQB1*0401 haplotype. Among subjects carrying the 
      CTLA-4 GG genotype, the frequency of IL-18 haplotype 1 in patients with type 1 
      diabetes was significantly higher than that in controls (91% vs. 71%, P=0.012). 
      However, IL-18 haplotype 1 was not frequent in patients who do not exhibit the 
      CTLA-4 high-risk genotype. These results suggest that the IL-18 gene polymorphism 
      is associated with a type 1 diabetes susceptibility, and there might be a 
      gene-gene interaction between IL-18 gene with susceptible CTLA-4 gene.
FAU - Ide, Akane
AU  - Ide A
AD  - The First Department of Internal Medicine, Graduate School of Biomedical 
      Sciences, Nagasaki University, Nagasaki, Japan.
FAU - Kawasaki, Eiji
AU  - Kawasaki E
FAU - Abiru, Norio
AU  - Abiru N
FAU - Sun, Fuyan
AU  - Sun F
FAU - Kobayashi, Masakazu
AU  - Kobayashi M
FAU - Fukushima, Tetsuya
AU  - Fukushima T
FAU - Takahashi, Ryoko
AU  - Takahashi R
FAU - Kuwahara, Hironaga
AU  - Kuwahara H
FAU - Kita, Atsushi
AU  - Kita A
FAU - Oshima, Katsuya
AU  - Oshima K
FAU - Uotani, Shigeo
AU  - Uotani S
FAU - Yamasaki, Hironori
AU  - Yamasaki H
FAU - Yamaguchi, Yoshihiko
AU  - Yamaguchi Y
FAU - Eguchi, Katsumi
AU  - Eguchi K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Autoimmun
JT  - Journal of autoimmunity
JID - 8812164
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Ctla4 protein, mouse)
RN  - 0 (Interleukin-18)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Antigens, CD
MH  - Antigens, Differentiation/*genetics
MH  - CTLA-4 Antigen
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 1/*genetics
MH  - Female
MH  - Genes, MHC Class II
MH  - Humans
MH  - Interleukin-18/*genetics
MH  - Japan
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - *Polymorphism, Genetic
MH  - Promoter Regions, Genetic
EDAT- 2004/01/08 05:00
MHDA- 2004/11/05 09:00
CRDT- 2004/01/08 05:00
PHST- 2004/01/08 05:00 [pubmed]
PHST- 2004/11/05 09:00 [medline]
PHST- 2004/01/08 05:00 [entrez]
AID - S0896841103001707 [pii]
AID - 10.1016/j.jaut.2003.10.001 [doi]
PST - ppublish
SO  - J Autoimmun. 2004 Feb;22(1):73-8. doi: 10.1016/j.jaut.2003.10.001.