Association of a genetic polymorphism in ectonucleotide pyrophosphatase/phosphodiesterase 1 with hepatitis C virus infection and hepatitis C virus core antigen levels in subjects in a hyperendemic area of Japan
- 78 Downloads
The clinical course of chronic hepatitis C virus (HCV) infection is strongly associated with insulin resistance and obesity. The K121Q polymorphism in the ectonucleotide pyrophosphatase/phosphodiesterase (ENPP)-1 gene and the rs7566605 genotype located near insulin-induced gene 2 have been shown to be associated with insulin resistance and obesity. This study examined whether the K121Q polymorphism in ENPP1 or the rs7566605 genotype is associated with the clinical course of HCV infection.
The relationships between the clinical characteristics of 469 anti-HCV antibody-seropositive subjects (353 were positive for HCV core antigen or RNA, whereas 116 were negative for HCV RNA) and the polymorphisms were analyzed.
No significant differences in body mass index, plasma glucose level, serum insulin level, and other biochemical markers were observed between subgroups of subjects with different genotypes at the K121Q polymorphism or rs7566605. The frequency of the homozygous wild-type genotype at K121Q in HCV carriers, however, was significantly higher than that in subjects who were negative for HCV RNA (84.5% vs. 75.9%; P < 0.05). Moreover, in HCV carriers, HCV core antigen levels in subjects homozygous for the wild-type genotype at K121Q were significantly higher than in heterozygous carriers of K121Q (5358 fmol/l vs. 4002 fmol/l; P = 0.04). In contrast, the rs7566605 genotype was not associated with hepatitis C viremia or with the HCV core antigen level.
The K121Q variant of ENPP1 may be associated with hepatitis C viremia and core antigen levels in HCV carriers.
Key wordshepatitis C virus ENPP1 insulin resistance viremia single nucleotide polymorphism HCV core antigen
Unable to display preview. Download preview PDF.
- 5.Kenny-Walsh E for the Irish Hepatology Research Group. Overweight and obesity, hepatic steatosis, and progression of chronic hepatitis C: a retrospective study on a large cohort of patients in the United States. J Hepatol 2004;40:147–154.Google Scholar
- 8.Bacci S, Ludovico O, Prudente S, Zhang YY, Di Paola R, Mangiacotti D, et al. The K121Q polymorphism of the ENPP1/PC-1 gene is associated with insulin resistance/atherogenic phenotypes, including earlier onset of type 2 diabetes and myocardial infarction. Diabetes 2005;54:3021–3025.PubMedCrossRefGoogle Scholar
- 23.Costanzo BV, Trischitta V, Di Paola R, Spampinato D, Pizzuti A, Vigneri R, Frittitta L. The Q allele variant (GLN121) of membrane glycoprotein PC-1 interacts with the insulin receptor and inhibits insulin signaling more effectively than the common K allele variant (LYS121). Diabetes 2001;50:831–836.PubMedCrossRefGoogle Scholar
- 28.Lyon HN, Emilsson V, Hinney A, Heid IM, Lasky-Su J, Zhu X, et al. The association of a SNP upstream of INSIG2 with body mass index is reproduced in several but not all cohorts. PLoS Genet 2007;27:627–633.Google Scholar
- 31.Goncales NS, Costa FF, VAssallo J, Concales FL. Diagnosis of hepatitis C virus in Brazilian blood donors using a reverse transcriptase nested polymerase chain reaction: comparison with enzyme immunoassay and recombinant protein immunoblot assay. Rev Inst Med Trop Sao Paulo 2000;42:263–267.PubMedGoogle Scholar