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      Identification of variants in NFKBIA and association analysis with hepatocellular carcinoma risk among chronic HBV patients.

      Human Mutation

      Risk Factors, Carcinoma, Hepatocellular, Polymorphism, Single Nucleotide, Mutation, Logistic Models, genetics, complications, Liver Neoplasms, Linkage Disequilibrium, I-kappa B Proteins, Humans, Hepatitis B, Chronic, Haplotypes, Genotype, Genetic Variation, Gene Frequency, DNA Mutational Analysis, chemistry, DNA

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          Abstract

          Human nuclear factor of kappa light chain gene enhancer in B cells inhibitor, alpha (NFKBIA) inhibits the action of NF-kappaB by forming a heterodimer with NF-kappaB, and preventing its translocation to the nucleus. We have sequenced a human NFKBIA full gene including -1000bp promoter region to identify its gene polymorphisms as a potential candidate gene for host genetic study of Hepatocellular Carcinoma (HCC). Nine novel single nucleotide polymorphisms (SNPs) and one GAA deletion were identified; two in promoter region (c.-673A>T, c.-642C>T), two in exon 1 (c.78G>A (Leu26Leu), c.81C>T (Asp27Asp)), three in introns (c.284T>A, c.1952A>G and c.2444C>T) and three in 3'UTR (c.2710-2712delGAA, c.2758G>A and c.3053G>A). Among ten identified variants, six were selected for larger scale genotyping (n=1,750) for association study based on frequencies and location. Haplotypes, their frequencies and linkage disequilibrium coefficients (/D'/) between SNP pairs were estimated. Allele frequencies of each SNPs and haplotypes were compared between patients with HCC and patients without HCC among HbsAg positives by logistic regression. As a conclusion, we could not find any significant association of NFKBIA variants with development of HCC among chronic hepatitis B patients. Copyright 2003 Wiley-Liss, Inc.

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          Journal
          14961554
          10.1002/humu.9146

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