Interferon-lambda genotype and low serum low-density lipoprotein cholesterol levels in patients with chronic hepatitis C infection.
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 = 6.0 x 10(-4)), apolipoprotein B (P = 1.3 x 10(-6)) and low-density lipoprotein (LDL) cholesterol (P = 8.9 x 10(-10)) were significantly higher in subjects carrying the rs12979860 CC responder genotype compared with those with the CT or TT genotype. Levels of triglycerides (P = 0.03), apolipoprotein A-I (P = 0.06), and apolipoprotein E (P = 0.01) were slightly lower in the rs12979860 CC genotype group, whereas levels of high-density lipoprotein cholesterol (P = 0.78) and apolipoprotein C-III (P = 0.74) did not vary by rs12979860 genotype.


CONCLUSIONS
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.
Institute for Genome Sciences and Policy, Durham, NC 27708, USA.
Josephine H
JH
Li
Xiang Qian
XQ
Lao
Hans L
HL
Tillmann
Jennifer
J
Rowell
Keyur
K
Patel
Alexander
A
Thompson
Sunil
S
Suchindran
Andrew J
AJ
Muir
John R
JR
Guyton
Stephen D
SD
Gardner
John G
JG
McHutchison
Jeanette J
JJ
McCarthy
D000328:Adult; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000097:blood / Q000235:genetics*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000095022:Interferon Lambda
D008078:Cholesterol, LDL; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda