Genetic Variation in the IL-6 and HLA-DQB1 Genes Is Associated with Spontaneous Clearance of Hepatitis C Virus Infection
Background. Millions of people are infected with hepatitis C virus (HCV) worldwide and 30% spontaneously clear the infection. Reasons for HCV clearance without antiviral treatment are not well understood. Methods. Blood was collected for DNA analysis from patients with chronic HCV infection or evide...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2016/6530436 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832564961647263744 |
|---|---|
| author | Paul Ravi Waldron Ilana Belitskaya-Lévy Aarthi Chary Johann Won Mark Winters Alexander Monto James Ryan Laura C. Lazzeroni Mark Holodniy |
| author_facet | Paul Ravi Waldron Ilana Belitskaya-Lévy Aarthi Chary Johann Won Mark Winters Alexander Monto James Ryan Laura C. Lazzeroni Mark Holodniy |
| author_sort | Paul Ravi Waldron |
| collection | DOAJ |
| description | Background. Millions of people are infected with hepatitis C virus (HCV) worldwide and 30% spontaneously clear the infection. Reasons for HCV clearance without antiviral treatment are not well understood. Methods. Blood was collected for DNA analysis from patients with chronic HCV infection or evidence of spontaneous clearance. To overcome anticipated limitations of small sample size, primary analyses consisted of a candidate gene analysis of 12 preselected genes based on known association with host immunologic response to HCV infection. To further reduce the impact of multiple testing on power, a single likelihood ratio test was conducted for each gene using all associated SNPs assayed on the Illumina Quad 610/660W chip. Step-down permutation methods were used to adjust for multiple testing in all analyses. Results. Ninety-five and 62 patients with HCV chronic infection or spontaneous clearance, respectively, were included for analysis. HLA-DQB1 (p=1.76⁎10-5) and IL-6 (p=0.0007) genes were significantly associated with spontaneous HCV clearance. IL-28B was not significantly associated with spontaneous clearance (p=0.17). Conclusion. Our whole-gene analytic strategy identified a previously unreported association of IL-6 with spontaneous clearance of HCV infection. We also confirmed the finding that HLA-DQB1 is associated with spontaneous resolution of HCV infection. |
| format | Article |
| id | doaj-art-6cb58682058a4b3e954d35e4a09c3318 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-6cb58682058a4b3e954d35e4a09c33182025-02-03T01:09:44ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/65304366530436Genetic Variation in the IL-6 and HLA-DQB1 Genes Is Associated with Spontaneous Clearance of Hepatitis C Virus InfectionPaul Ravi Waldron0Ilana Belitskaya-Lévy1Aarthi Chary2Johann Won3Mark Winters4Alexander Monto5James Ryan6Laura C. Lazzeroni7Mark Holodniy8VA Palo Alto Health Care System, Palo Alto, CA 94304, USACooperative Studies Program Coordinating Center, VA Palo Alto Health Care System, Palo Alto, CA 94304, USAVA Palo Alto Health Care System, Palo Alto, CA 94304, USACooperative Studies Program Coordinating Center, VA Palo Alto Health Care System, Palo Alto, CA 94304, USAVA Palo Alto Health Care System, Palo Alto, CA 94304, USASan Francisco VA Medical Center, San Francisco, CA 94121, USASan Francisco VA Medical Center, San Francisco, CA 94121, USACooperative Studies Program Coordinating Center, VA Palo Alto Health Care System, Palo Alto, CA 94304, USAVA Palo Alto Health Care System, Palo Alto, CA 94304, USABackground. Millions of people are infected with hepatitis C virus (HCV) worldwide and 30% spontaneously clear the infection. Reasons for HCV clearance without antiviral treatment are not well understood. Methods. Blood was collected for DNA analysis from patients with chronic HCV infection or evidence of spontaneous clearance. To overcome anticipated limitations of small sample size, primary analyses consisted of a candidate gene analysis of 12 preselected genes based on known association with host immunologic response to HCV infection. To further reduce the impact of multiple testing on power, a single likelihood ratio test was conducted for each gene using all associated SNPs assayed on the Illumina Quad 610/660W chip. Step-down permutation methods were used to adjust for multiple testing in all analyses. Results. Ninety-five and 62 patients with HCV chronic infection or spontaneous clearance, respectively, were included for analysis. HLA-DQB1 (p=1.76⁎10-5) and IL-6 (p=0.0007) genes were significantly associated with spontaneous HCV clearance. IL-28B was not significantly associated with spontaneous clearance (p=0.17). Conclusion. Our whole-gene analytic strategy identified a previously unreported association of IL-6 with spontaneous clearance of HCV infection. We also confirmed the finding that HLA-DQB1 is associated with spontaneous resolution of HCV infection.http://dx.doi.org/10.1155/2016/6530436 |
| spellingShingle | Paul Ravi Waldron Ilana Belitskaya-Lévy Aarthi Chary Johann Won Mark Winters Alexander Monto James Ryan Laura C. Lazzeroni Mark Holodniy Genetic Variation in the IL-6 and HLA-DQB1 Genes Is Associated with Spontaneous Clearance of Hepatitis C Virus Infection Journal of Immunology Research |
| title | Genetic Variation in the IL-6 and HLA-DQB1 Genes Is Associated with Spontaneous Clearance of Hepatitis C Virus Infection |
| title_full | Genetic Variation in the IL-6 and HLA-DQB1 Genes Is Associated with Spontaneous Clearance of Hepatitis C Virus Infection |
| title_fullStr | Genetic Variation in the IL-6 and HLA-DQB1 Genes Is Associated with Spontaneous Clearance of Hepatitis C Virus Infection |
| title_full_unstemmed | Genetic Variation in the IL-6 and HLA-DQB1 Genes Is Associated with Spontaneous Clearance of Hepatitis C Virus Infection |
| title_short | Genetic Variation in the IL-6 and HLA-DQB1 Genes Is Associated with Spontaneous Clearance of Hepatitis C Virus Infection |
| title_sort | genetic variation in the il 6 and hla dqb1 genes is associated with spontaneous clearance of hepatitis c virus infection |
| url | http://dx.doi.org/10.1155/2016/6530436 |
| work_keys_str_mv | AT paulraviwaldron geneticvariationintheil6andhladqb1genesisassociatedwithspontaneousclearanceofhepatitiscvirusinfection AT ilanabelitskayalevy geneticvariationintheil6andhladqb1genesisassociatedwithspontaneousclearanceofhepatitiscvirusinfection AT aarthichary geneticvariationintheil6andhladqb1genesisassociatedwithspontaneousclearanceofhepatitiscvirusinfection AT johannwon geneticvariationintheil6andhladqb1genesisassociatedwithspontaneousclearanceofhepatitiscvirusinfection AT markwinters geneticvariationintheil6andhladqb1genesisassociatedwithspontaneousclearanceofhepatitiscvirusinfection AT alexandermonto geneticvariationintheil6andhladqb1genesisassociatedwithspontaneousclearanceofhepatitiscvirusinfection AT jamesryan geneticvariationintheil6andhladqb1genesisassociatedwithspontaneousclearanceofhepatitiscvirusinfection AT lauraclazzeroni geneticvariationintheil6andhladqb1genesisassociatedwithspontaneousclearanceofhepatitiscvirusinfection AT markholodniy geneticvariationintheil6andhladqb1genesisassociatedwithspontaneousclearanceofhepatitiscvirusinfection |