Importance of IL28B gene polymorphisms in hepatitis C virus genotype 2 and 3 infected patients.
OBJECTIVE
Genetic variation in the interleukin 28B (IL28B) gene has been associated with the response to interferon-alfa/ribavirin therapy in hepatitis C virus (HCV) genotype 1-infected patients. The importance of three IL28B single nucleotide polymorphisms (rs8099917, rs12980275 and rs12979860) for HCV genotype 2/3-infected patients is unknown.


METHODS
In patients with chronic hepatitis C genotype 2/3 (n=267), IL28B host genotypes (rs8099917, rs12980275 and rs12979860) were analyzed for associations with sustained virologic response (SVR) to antiviral therapy with (pegylated) interferon-alfa and ribavirin and with respect to epidemiological, biochemical, and virological parameters. For comparison, hepatitis C genotype 1 patients (n=378) and healthy controls (n=200) were included.


RESULTS
The rs12979860 CC genotype, lower age, and genotype 2 were significantly associated with SVR in HCV genotype 2/3-infected patients (p=0.01, p=0.03 and p=0.03, respectively). No association was observed for rs8099917 and rs12980275. In addition, an SVR in patients with rapid virologic response (RVR) was associated with the rs12979860 CC genotype (p=0.05), while for non-RVR no association was found. Furthermore, a significant association with a higher baseline viral load was observed for all three IL28B genotypes in genotype 1/2/3-infected patients. Finally, increasing frequencies of the rs12979860 CC genotypes were observed in genotype 1- (33.9%), genotype 3- (38.9%), and genotype 2-infected (51.9%) patients in comparison with healthy controls (49.0%) (p<0.01).


CONCLUSIONS
In genotype 2/3-infected patients, rs12979860 was significantly associated with SVR. The frequency of the rs12979860 CC genotype is lower in HCV genotype 1 vs. genotype 2/3 patients. All major IL28B genotypes are associated with HCV-RNA concentration.
Medizinische Klinik 1, J. W. Goethe-University Hospital, Frankfurt am Main, Germany. sarrazin@em.uni-frankfurt.de
Christoph
C
Sarrazin
Simone
S
Susser
Alexandra
A
Doehring
Christian Markus
CM
Lange
Tobias
T
Müller
Christina
C
Schlecker
Eva
E
Herrmann
Jörn
J
Lötsch
Thomas
T
Berg
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005858:Germany; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D019562:Viral Load; D000095022:Interferon Lambda
D000410:Alanine Transaminase; D000998:Antiviral Agents; D017931:DNA Primers; D007370:Interferon Type I; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda