| Project/Area Number |
12670519
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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 | JIKEI UNIVERSITY SCHOOL OF MEDCINE |
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Principal Investigator |
WATANABE Fumitoki JIKEI UNIVERSITY SCHOOL OF MEDICINE, DIVIGION OF GASTROENTEROLOGY AND HEPATOLOGY. DEPARTMENT OF INTERNAL MEDICINE, LECTURELAR, 医学部, 講師 (90231711)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Hiroki JIKEI UNIVERSITY SCHOOL OF MEDICINE,DIVIGION OF GASTROENTEROLOGY AND HEPATOLOGY, DEPARTMENT OFINTERNAL MEDICINE, ASSISTANT, 医学部, 助手 (80256403)
ZENIYA Mikio JIKEI UNIVERSITY SCHOOL OF MEDICINp, DIVIGION OF GASTROENTEROLOGY AND HEPATOLOGY, DEPARTMENT OF INTERNAL MEDICINE, AS SISTANT PROFESSOR, 医学部, 助教授 (70138767)
TODA Gotaro JIKEI UNIVERSITY SCHOOL OF MEDICINE, DIVIGION OF GASTROENTEROLOGY AND HEPATOLOGY, DEPARTMENT OF INTERNAL MEDICINE, PROFESSOR, 医学部, 教授 (40090500)
林 昭太 東京慈恵会医科大学, 医学部, 助手 (80287276)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | AIH / PEC / POLYMORPHISM / CTLA-4 / IFN-γ / 疾患感受性遺伝子 |
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| Research Abstract |
Background and Aim: The etiology of autoimmune liver disease (AILD) such as autoimmune hepatitis (AIH) or primary biliary cirrhosis (PBC) appears toinvolve a complex interplay of multiple genetic and environmental factors.The aim of this study is to investigate whether frequency of gene polymorphism in GTLA-4 and IFN-y may influence disease susceptibility and clinical manifestations of AILD in Japanese population.
Patients and Methods: 101 clinically and pathologically diagnosed PBC patients, 5 1 AIH patients and 84 controls were studied. The CTLA-4 exon 1 position 49 A/G polymorphism was typed using RFLP method. The IFN-y position 874 A/T polymorphism was defined by amplification refractory mutational system (ARMS) PCR method.
Results: The analysis of CTLA-4 polymorphism revealed that there were significant over representation of the G/G genotype inpatients compared to controls (G/G 57.3% vs, 40.4%; A/G 34.8% vs. 50.0%; A/A7.9% vs. 9.6%, OR= 1.97, 95% CI : 1.1-3.6, p<0.04). The AAgenotype was associated with a significantly lower serum ALP level than other genotypes(p<0. 05). The analysis of IFN-y polymorphism revealed that there were significant over representation of the T/A genotype in patients compared to controls (T/A 34.4% vs. 19.0%; A/A 65.6% vs. 81.0%, OR = 2.23, 95% CI :1.1-4.4, p<0.03). The inclusive study made clear that the risk for PBC of individuals carrying both CTLA-4 G/G and IFN-y T/A genotype (OR=5.23) was higher compared with the risks conferred by CTLA-4 G/G or IFN-y T/A alone (OR=2.34, 2.95). Tnis indicated that the effect ofth」 CTLA-4 G/G and the IFN-yT/A genotype on susceptibility to PBC was additive.
Conclusion: Genetic polymorphisms of non-HLA molecules (CTLA-4, IFN-y) were related to susceptibility to Japanese PBC and were associated with certain clinical features. Especially CTLA-4 and IFN-y gene polymorphism confer susceptibility to PBC and were associated with the efficacy of UD CA tre atment additively.
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