Association between IL-18 gene promoter polymorphisms and inflammatory bowel disease in a Japanese population.
BACKGROUND
Interleukin-18 (IL-18) is a pleiotropic cytokine that induces the production of interferon (IFN)-gamma and also to regulate Th2 cytokines. Recently, association studies between IL-18 gene promoter polymorphisms and several Th1- or Th2-mediated inflammatory diseases were reported. In inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), recent evidence suggests that IL-18 is involved in the pathogenesis.


METHODS
Using DNA direct sequencing, we investigated IL-18 gene promoter polymorphisms at -607C/A and -137G/C. Allele, genotype, and haplotype frequencies were determined in 210 Japanese patients with UC, 205 patients with CD, and 212 controls.


RESULTS
In UC, the -137C allele frequency was significantly higher in the proctitis-type patients than in controls (Pc = 0.0068). The -137 genotype frequency was also significantly different in the proctitis-type patients than in controls (Pc = 0.032). No other allele and genotype frequencies were significantly associated with UC after Bonferroni correction. Furthermore, the frequency of haplotype 2 (-607A, -137C), which had a lower promoter activity and IFN-gamma mRNA level than the other haplotypes as previously reported, was significantly higher in the proctitis-type patients than in controls (Pc = 0.01). In CD, we could not find any significant differences.


CONCLUSIONS
IL-18 gene promoter polymorphisms may not be associated with disease susceptibility but related to the extent of disease in UC.
Takagawa
T
T
Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Tamura
K
K
Takeda
N
N
Tomita
T
T
Ohda
Y
Y
Fukunaga
K
K
Hida
N
N
Ohnishi
K
K
Hori
K
K
Kosaka
T
T
Fukuda
Y
Y
Ikeuchi
H
H
Yamamura
T
T
Miwa
H
H
Matsumoto
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
D020382:Interleukin-18