Interferon-Lambda Genotype and Low Serum Low-Density Lipoprotein Cholesterol Levels in Patients With Chronic Hepatitis C Infection

Abstract

Recently, genetic polymorphisms occurring in the interferon (IFN)-lambda gene region were associated with response to IFN-based treatment of hepatitis C infection. Both infection with the hepatitis C virus and IFN therapy are associated with decreased serum cholesterol and high cholesterol has been associated with increased likelihood to respond to IFN. We sought to determine if the IFN-lambda gene variant was also associated with serum lipid levels in chronic hepatitis C patients. We compared genotypes of the rs12979860 polymorphism, located proximal to the IL28 gene, with serum lipid and apolipoprotein levels in 746 subjects with chronic hepatitis C virus infection, not currently undergoing treatment, using multivariable analysis of variance. Levels of total cholesterol (P 5 6.0 3 10 24 ), apolipoprotein B (P 5 1.3 3 10 26) and low-density lipoprotein (LDL) cholesterol (P 5 8.9 3 10 210 ) were significantly higher in subjects carrying the rs12979860 CC responder genotype compared with those with the CT or TT genotype. Levels of triglycerides (P 5 0.03), apolipoprotein A-I (P 5 0.06), and apolipoprotein E (P 5 0.01) were slightly lower in the rs12979860 CC genotype group, whereas levels of high-density lipoprotein cholesterol (P 5 0.78) and apolipoprotein C-III (P 5 0.74) did not vary by rs12979860 genotype. Conclusion: Our results suggest that low levels of LDL cholesterol in chronic hepatitis C patients may be a marker of host endogenous IFN response to hepatitis C and that subjects with the rs12979860 CC responder genotype may have a lower endogenous IFN response to the virus. (HEPATOLOGY 2010;51:1904-1911

Genetic variation in the interleukin - 28B gene is not associated with fibrosis progression in patients with chronic hepatitis C and known date of infection

“…PEG-IFN/RBV), compared to those carrying the T allele (C/T and T/T genotypes). More recently, it has also been proposed that the poor response IL28B variants, in hepatitis C patients, are also associated with lower pretreatment low-density lipoprotein cholesterol levels, 17,18 hepatic steatosis, 18,19 and insulin resistance, 19 compared to the ''responder'' genotype. However, it is still unclear whether the genetic variation at the IL28B locus affects the severity and pace of the progression of liver disease.…”

IL28B in hepatitis C virus infection: translating pharmacogenomics into clinical practice

“…Other groups have investigated the impact of IL28B host polymorphisms on lipid metabolism in patients with chronic HCV infection and noted an association of the responder genotype with higher levels of total cholesterol, apo-lipoprotein B, and low-density lipoprotein (LDL) [19]. In the context of liver transplantation, Eurich et al [20] have reported that rs8099917 influences the biochemical and histological levels of graft inflammation, though not the progression to fibrosis in patients with recurrent HCV infection post-transplant.…”

Dysregulation of distal cholesterol biosynthesis in association with relapse and advanced disease in CHC genotype 2 and 3 treated with sofosbuvir and ribavirin

“…Due to the relatively small cohort, we were not able to demonstrate genotype-specific differences in baseline lathosterol levels and virologic response among cirrhotic patients. Other host variables such as IFNL3 gene variants have been associated with higher levels of LDL-C and ApoB for HCV GT1 but not GT3 [54]. However, there was no association between IFNL3 rs12979860 genotype with relapse in our cohort, and was not further evaluated in relation to sterol intermediates.…”