Genetic variation in the IKK/NF-B pathway and the live fibrosis progression in chronic hepatitis C R. Sho 1 , K. Ishii 1 , R. Ishii 2 , H. Watanabe 2 , K. Sugahara 2 , Y. Nishise 2 , K. Okumoto 2 , T. Saito 2 , S. Kawata 2 , A. Fukao 1 1 Department of Public Health, 2 Department of Gastroenterology, Yamagata University Faculty of Medicine Background/Aims: I B kinase/NF-B (IKK/NF-B) signaling pathway is thought to play critical roles in liver inflammation and fibrogenesis. We carried out a haplotype-based association study to examine the contribution of common genetic variations in the genes encoding NF B inhibitor kinase alpha and beta (IKBKA and IKBKB; the major components of IKK/NF-B pathway) to the progression of live fibrosis in chronic hepatitis C. Methods: Based upon the common single nucleotide polymorphisms (SNPs; minor allele frequency(MAF) 0.05) and linkage disequilibrium (LD) information derived from the HapMap, we selected 5 and 3 tag SNPs from IKBKA, and IKBKB, respectively, for genotyping. By using melting curve analysis, SNPs were genotyped in 217 chronic hepatitis C patients, including 80 patients with hepatocellular carcinoma. Association between common genetic variations in IKBKA/IKBKA and platelet count (Plt) was tested by both genotype-and haplotype-based approaches. Results: We succeeded in genotyping a total of 8 tag SNPs that efficiently capture common variation across the 32 kb-block of IKBKA and the 25 kb-block of IKBKB. For each of genes tested, 5 haplotypes were found in population studied. All SNPs were in Hardy-Weinberg equilibrium, but no significant association was observed between any single tag SNP or haplotype and decreased Plt in patients analyzed. Conclusions: Our data suggest that it is unlikely that polymorphisms within the IKBKA and IKBKB genes are involved in the progression of live fibrosis in chronic hepatitis C. Further studies on genetic variations in other NF-B-related genes in chronic hepatitis C are needed.