Genetic Variation Associated with Chronic Hepatitis C in Women

Research increasingly shows that host genetic variations influence hepatitis C disease progression and response to treatment.

According to a study reported in the September 2006 Journal of Virology, a specific polymorphism (genetic variation at a single site) is associated with liver disease progression in women infected with the hepatitis C virus (HCV).

Previous research has shown that levels of the cytokine interleukin 10 (IL-10) are elevated in patients with chronic hepatitis C, compared with those who are able to spontaneously clear the virus without treatment.

In the current study, researchers from Argentina used a sequence-specific oligonucleotide probing technique to analyze variations in a gene associated with IL-10 production in 286 hepatitis C patients grouped according to disease outcome.

The GG genotype pattern is known to be associated with high IL-10 production, while the GA genotype is associated with intermediate production, and the AA genotype with low production.

Results

The GG genotype pattern was more common among female patients who did not eliminate HCV (i.e., who were chronically HCV RNA-positive).

In these patients, the GG frequency was 0.19, compared with 0.10 among control subjects (P = 0.03).

This association was more significant when looking at HCV RNA-positive women with elevated hepatic transaminase (ALT and AST) levels, who had a GG frequency of 0.25 (P = 0.0013).

However, the GG genotype was also more common among non-cirrhotic women, who had a frequency of 0.31 (P = 0.009).

Among HCV RNA-negative patients, the frequency of the GA genotype pattern was elevated compared with controls (0.76 vs 0.48; P = 0.01), HCV patients as a whole (0.43; P = 0.001), and HCV RNA-positive patients (0.40; P = 0.0005).

Conclusion

"We conclude that a gender effect is observed with women carrying the GG high IL-10 producer genotype," the authors wrote. "The higher levels of IL-10 present in those individuals are associated with a higher risk of an inefficient clearance of HCV and the development of a chronic HCV infection together with a lower risk of progression to cirrhosis in female patients."

It remains unclear why the high IL-10 genotype pattern would be associated with both inefficient clearance of HCV and also with a lower likelihood of progression to cirrhosis.

09/08/06

Reference
N Paladino, H Fainboim, G Theiler, and others. Gender susceptibility to chronic hepatitis C virus infection associated with interleukin 10 promoter polymorphism. Journal of Virology 80(18): 9144-9150. September 2006.