| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Research Abstract |
Primary biliary cirrhosis (PBC) is a chronic and slowly progressing autoimmune liver disease characterized histopathologically by inflammation and destruction of the intrahepatic small bile ducts, thus resulting in cholestasis and thereby leading to hepatic damage, cirrhosis, and eventually hepatic failure. Although the precise etiology of PBC remains unknown, both several environmental factors and multiple genetic factors may contribute to the pathogenesis as well as progression of PBC. As we focused on 26 candidate genes related with the homeostasis of bile acid and normal bile duct formation, a candidate gene-based association study on susceptibility to the progression of PBC was carried out using 109 single nucleotide polymorphisms in the 26 candidate genes for 333 Japanese PBC patients.
Chi-square test or Fisher's exact test revealed that the 7 genes, CYP7A1, CYP8B1, HNF4A, PPARGC1A, RXRB, ASBT, and ABCG8, were associated with susceptibility to the progression to cirrhosis, and that the 6 genes, CYP7A1, PPARGC1A, RXRB, FGF19, MDR3, ABCG8, and ITGAV, appeared to be susceptible to severe progression to haptic failure with jaundice. Furthermore, a combination of polymorphisms of CYP8B1 and PPARGC1A is a useful biomarker for identifying high-risk PBC patients for progression to cirrhosis. Likewise, a combination of polymorphisms of CYP7A1, PPARGC1A, ABCG8, and ITGAV is useful as the best biomarker for severe progression to haptic failure with jaundice.
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