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Journal of Virology, May 2004, p. 4561-4565, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4561-4565.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Epistatic Effects of Immunoglobulin GM and KM Allotypes on Outcome of Infection with Hepatitis C Virus

Janardan P. Pandey,1* Jacquie Astemborski,2 and David L. Thomas2

Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina,1 Department of Medicine, Johns Hopkins University, Baltimore, Maryland2

Received 13 October 2003/ Accepted 7 December 2003

Immunoglobulin GM and KM allotypes—genetic markers of {gamma} and {kappa} chains, respectively—are associated with immune responsiveness to several infectious pathogens and with survival in certain viral epidemics. We hypothesized that GM and KM allotypes affect the outcome of hepatitis C virus (HCV) infection. To test this hypothesis, we serologically allotyped 100 persons with well-documented clearance of HCV infection and 198 matched persistently infected persons. None of the GM or KM phenotypes by itself was associated with the clearance or persistence of HCV infection. Particular combinations of these phenotypes, however, were significantly associated with the outcome of HCV infection. Subjects with GM 1,17 5,13 and KM 1,3 phenotypes were over three times (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.44 to 8.87) as likely to clear the infection as the subjects who lacked these phenotypes. This GM phenotype had a similar association with clearance in the absence of KM 3 (OR, 2.75; 95% CI, 1.21 to 6.23). The presence of GM 1,3,17 23 5,13 phenotype (in the absence of KM 3) was associated with persistence (OR, 0.21; 95% CI, 0.06 to 0.77), while its absence (in the presence of KM 1,3) was associated with the clearance of infection (OR, 2.03; 95% CI, 1.16 to 3.54). These results show epistatic interactions of genes on chromosomes 14 (GM) and 2 (KM) in influencing the outcome of an HCV infection. Further investigations involving candidate genes (GM, KM, HLA, and Fc{gamma} receptors) and cellular and humoral immune responses to HCV epitopes are needed to understand the mechanisms underlying these associations.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425-2230. Phone: (843) 792-4360. Fax: (843) 792-2464. E-mail: pandeyj{at}musc.edu.

Journal of Virology, May 2004, p. 4561-4565, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4561-4565.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Muratori, P., Sutherland, S. E., Muratori, L., Granito, A., Guidi, M., Pappas, G., Lenzi, M., Bianchi, F. B., Pandey, J. P. (2006). Immunoglobulin GM and KM Allotypes and Prevalence of Anti-LKM1 Autoantibodies in Patients with Hepatitis C Virus Infection.. J. Virol. 80: 5097-5099 [Abstract] [Full Text]  


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