IL18 polymorphism is associated with an increased risk of Crohn's disease.
BACKGROUND
The etiology of inflammatory bowel disease, which includes ulcerative colitis and Crohn's disease, has not yet been made clear. However, inflammatory bowel disease is recognized as a multifactorial disease, and innate genetic factors might contribute to the pathogenesis. Cytokine genes are thought to be important in inflammatory bowel disease. Recently, interleukin 18, cloned as a novel proinflammatory cytokine, has been implicated in inflammatory bowel disease, especially Crohn's disease.


METHODS
To identify germline mutations in patients with inflammatory bowel disease, the entire coding region of IL18 was examined using a DNA sequencing procedure.


RESULTS
No functional mutations were found, but a novel single nucleotide polymorphism (SNP) was identified as TCA/TCC at codon 35. In patients with Crohn's disease, the frequency of TCC allele carriers was significantly higher than in healthy controls (chi2 = 9.35, P = 0.002229, OR = 2.58, 95% CI = 1.39-4.80). Also, the magnitude of the association was more remarkable in females (chi2 = 16.36, P = 0.000052, OR = 8.17, 95% CI = 2.73-24.41). The TCC allele at codon 35 of IL18 may increase the risk for Crohn's disease, especially in females.


CONCLUSIONS
IL18 is probably one of several genes that determine susceptibility to Crohn's disease.
Tamura
Kazuo
K
Laboratory of Hereditary Tumor, Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya 663-8501, Japan.
Fukuda
Yoshihiro
Y
Sashio
Hiroko
H
Takeda
Naohisa
N
Bamba
Hiroko
H
Kosaka
Tadashi
T
Fukui
Shin
S
Sawada
Koji
K
Tamura
Kazutami
K
Satomi
Masamichi
M
Yamada
Takahiro
T
Yamamura
Takehira
T
Yamamoto
Yoshihiro
Y
Furuyama
Jun-ichi
J
Okamura
Haruki
H
Shimoyama
Takashi
T
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics*; D016001:Confidence Intervals; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D020382:Interleukin-18 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016017:Odds Ratio; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D017678:Sex Distribution
D020382:Interleukin-18