IL28B Gene Variation Associated with Lipid Levels in People with HIV/HCV Coinfection

		SUMMARY: HIV/HCV coinfected individuals who carry the protective C/C variation of the IL28B gene have higher levels of total and LDL ("bad") cholesterol but lower levels of HDL ("good") cholesterol, according to a study presented this week at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010) in Boston. Because cholesterol and its receptors play an important role in the hepatitis C virus (HCV) lifecycle, these findings may help explain why IL28B is linked to spontaneous viral clearance and better response to interferon-based therapy.

By Liz Highleyman

In 2009, researchers first reported that a specific variation or polymorphism (dubbed C/C) in the IL28 gene -- which encodes interleukin 28, also known as interferon lambda -- was associated with both spontaneous clearance of HCV and better response to interferon-based therapy for chronic infection in HIV negative people. At this year's Conference on Retroviruses and Opportunistic Infections (CROI 2010), a series of reports showed similar results for HIV/HCV coinfected patients.

At ICAAC, Norma Rallon from Hospital Carlos III in Madrid and colleagues presented data from a study looking at the association between the IL28B rs12979860 single nucleotide polymorphism (a change at a specific location in the genome) and lipid levels in people with HIV/HCV coinfection.

Serum lipid levels in chronic hepatitis C patients have been linked to greater likelihood of sustained virological response (SVR) to interferon, the investigators noted as background. HCV particles attach themselves to lipoproteins in the blood and use the LDL surface receptor to enter cells.

This study included 164 HIV/HCV coinfected patients at a single clinic in Madrid who completing therapy with pegylated interferon plus ribavirin and had validated outcomes.

The rs12979860 polymorphism was examined using allele specific TaqMan probes. The researchers then looked at associations with levels of total, low density lipoprotein (LDL), very low density lipoprotein (VLDL), and high density lipoprotein (HDL) cholesterol.

Results

" 90 study participants achieved SVR and 74 were non-responders.
" The protective rs12979860 C/C gene pattern was significantly associated with higher baseline levels of total, LDL, and VLDL cholesterol, but lower levels of HDL cholesterol after adjusting for other factors.
" In a univariate (single-factor) analysis, the C/C pattern was significantly associated with SVR, confirming prior research.
" There was a trend toward an association between SVR and elevated lipid levels, but this did not reach statistical significance.
" In a multivariate analysis controlling for multiple factors, only the C/C genotype -- but not lipid levels -- was significantly associated with SVR independent of other baseline factors.

Based on these findings, the investigators concluded, "In HIV/HCV coinfected patients the C/C IL28B genotype significantly influences pre-treatment levels of LDL, VLDL, HDL, and total cholesterol."

However, they added, "The biological mechanism of this association remains to be determined."

Investigator affiliations: Hosp. Carlos III, Madrid, Spain; Duke Clinical Res. Institute, Durham, NC; Institute for Genome Science and Policy, Durham, NC.

9/14/10

Reference
NI Rallon, E Vispo, JM Benito, and others. IL28b (IFN-lambda3) Polymorphism Significantly Influences Pre-treatment Lipid Levels In Hiv/hepatitis C Virus-coinfected Patients. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010). Boston, September 12-15, 2010. (Abstract H-1669).