1997 Fiscal Year Final Research Report Summary
Significance of cytokine gene polymorphisms in the development of severe alcoholic liver disease
| Project/Area Number |
08670628
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | The Jikei University School of Medicine |
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Principal Investigator |
YAMAUCHI Masayoshi The jikei Universitu School of Medicine, First Department of Internal of Medicine, Associate Professor, 医学部, 講師 (20138811)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUHARA Yuji The jikei University School of Medicine, First Department of Internal of Medicin, 医学部, 助手 (20266688)
NISHIKAWA Fuminori The jikei University School of Medicine, First Department of Internal of Medicin, 医学部, 助手 (20266662)
OHATA Mitsuru The jikei University School of Medicine, First Department of Internal of Medicin, 医学部, 助手 (50231204)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Alcoholic liver disease / Cytokine gene polymorphism / TNF gene polymorphism / IL-1 Receptor antagonist / IL-1 beta gene |
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| Research Abstract |
Severe alcoholic liver disease such as cirrhosis and alcoholic hepatitis develop in some alcoholics. In this study, we investigated the correlation between polymorphisms in the cytokine genes and Japanese alcoholic liver disease.
(1) Interleukin-1 receptor antagonist (IL-1-Ra) gene : The distribution of IL1-Ra genotype and the allelic frequencies in Japanese healthy subjects were both significantly different from that previously reported in Caucasian 8A1/A1 genotype : 95.7% in Japanese vs.54.0% in Caucasians, A1 allele ; 97.8% vs.73.4%, p<0.001). The frequency of A1 heterozygotes tended to be higher in Japanese alcoholics with fibrosis compared to yhose without fibrosis (14.9% vs.2.9%). In the fibrotic groups cumulative alcohol intake was significantly lower in A1 heterozygotes than in the A1 homozygotes. (2) TNF gene : We examined the frequency of the two recently described polymorphisms of the TNF alpha promoter in patients with alcoholic liver disease and the healthy subjects. However, no polymorphisms of the TNF alpha gene was found in Japanese. The frequency of TNF beta genotype using NcoI (+/+, +/-, -/-) was (11.4%, 51.4%, 37.2%) in the non-fibrotic group, (9.0,58.2,32.8) in the fibrotic group, and (25.0,62.5,12.5) in the patients with alcoholic hepatitis, respectively. (3) IL-1 beta gene : We investigated the two polymorphic sites of the IL-1 beta gene located in the exon 1 and -511 locus. However, no association was found between IL-1 beta polymorphism and the developmemt of severe alcoholic liver disease.
Therefore, We are now going on the study for the IL-10 and TNF receptor gene polymorphisms and seaquence analysis of endotoxin receptor (CD14) in the patients with severe alcoholic liver disease.
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