Rubin, D., Vollbrecht, H., Ross, S., Nasser, S., Gunther, R., Buggisch, P., Hinrichsen, H., Ruether, A., Ulf, H., Nitz, I., Doering, F., Nothnagel, M., Schreiber, Stefan, Folsch, U. R. and Schrezenmeir, J. (2009) Caveolin-2 Q130e Gene Polymorphism Is Highly Associated with Response to Antiviral Therapy in Hepatitis C and Clinical Features of Hepatic Steatosis. Journal of Hepatology, 50 . S327-S327. DOI 10.1016/S0168-8278(09)60902-8.

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Abstract

The natural course and response to antiviral therapy in chronic hepatitis C is apart from attributes of the virus itself influenced by features of the individual patient’s comorbidities and host genetic factors. Hepatic steatosis, adipositas and elevation of GGT are known as negative predictors for treatment response. Genes involved in fatty acid partitioning and binding are overexpressed in human fatty liver. Publications over the last years give increasing insight into the role of lipid metabolism in the life cycle and replication of hepatitis c virus. Caveolin 2 is a candidate gene for hepatic lipid accumulation and insulin resistance. Caveolin2 expression is regulated by insulin and overexpression of caveolin2b leads to constitutive localization on the surface of lipid droplets. A total of 704 male subjects from a postprandially characterized cohort (MICK) were genotyped for the CAV Q130E exon polymorphism. Increased liver enzymes were used as surrogates for non-alcoholic hepatic steatosis. The genetic variant was tested for association with insulin resistance, lipid parameters and clinical features of hepatic steatosis. The same polymorphism was tested in a 138 patient group infected with hepatitis C. We investigated an association with response to antiviral therapy, spontaneous viral elimination and, in the long-term chronically infected patients, the stage of fibrosis. In comparison of the homozygote subjects of the common allele, carriers of the rare allele 130E showed significantly lower levels of alanine aminotransferase and aspartat aminotransferase (12.83±6.95 vs., 14.78±9.36, p=0.005; 8.47±3.22 vs. 9.35±5.22, p=0.02) and higher HDL cholesterol levels (54.75±15.04 vs. 52.69±14.56, p=0.03). HCV infected carriers of the 130E mutation responded to antiviral therapy in 80% compared to 57% in carriers of the common Q130Q allele (p=0.02). These results suggest a protective role of the 130E variant of the caveolin 2 gene against traits of the metabolic syndrome and consecutive hepatic steatosis. Consistently an association to the response to antiviral therapy could be demonstrated. In clinical practice the SNP may be useful as a predictor for the efficacy of an IFN-based antiviral therapy.

Document Type:	Article
Additional Information:	Suppl. 1450EV
Research affiliation:	Kiel University OceanRep > The Future Ocean - Cluster of Excellence
Refereed:	Yes
Open Access Journal?:	No
Publisher:	Elsevier
Projects:	Future Ocean
Date Deposited:	11 Feb 2011 12:15
Last Modified:	23 Sep 2019 20:34
URI:	https://oceanrep.geomar.de/id/eprint/9683

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