SNPs in the promoter region of the osteopontin gene as a possible host factor for sex difference in hepatocellular carcinoma development in patients with HCV

作者:Hamaoka Kazuhiro; Nagoshi Sumiko; Sugawara Kayoko; Naiki Kayoko; Uchida Yoshihito; Inao Mie; Nakayama Nobuaki; Fujiwara Kenji; Mochida Satoshi*
来源:Hepatology International, 2013, 7(2): 683-692.
DOI:10.1007/s12072-012-9404-1

摘要

Four single nucleotide polymorphisms (SNPs) exist in the promoter region of the osteopontin (OPN) gene, namely, the SNPs at nucleotide (nt) -155, -616, and -1748 showing linkage disequilibrium to each other, and an independent SNP at nt -443. The significance of these SNPs in the risk of hepatocellular carcinoma (HCC) development was examined in patients with hepatitis C virus (HCV). %26lt;br%26gt;The SNPs at nt -155 and nt -443 were analyzed in 120 patients with HCC. The promoter activity was measured in HepG2 cells by the dual-luciferase reporter assay. The electrophoretic mobility shift assay was performed using nuclear extracts from the cells. %26lt;br%26gt;Peripheral platelet counts at the time of HCC detection were greater in women with homozygous deletion at nt -155 and C/C or C/T at nt -443 than in those showing other allelic combinations, while no such difference was observed in men. The promoter activity was greater in oligonucleotides with deletions at nt -155 and C at nt -443 than in those with other haplotypes. The mobility shift assay showed double and single complexes with oligonucleotides around nt -155 and nt -443, respectively. Binding activities were greater in deletion than in G in the case of the retarded complex in the former assay and in T than in C in the latter assay. The other complex in the former assay included SRY, showing an equivalent binding activity to oligonucleotides with both alleles. %26lt;br%26gt;OPN promoter SNPs may play a role in the sexual difference in the risk of HCC development through the regulation of OPN expression in patients with HCV.

  • 出版日期2013-6

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