TY - JOUR
T1 - Large-scale candidate gene analysis of spontaneous clearance of hepatitis C virus
AU - Mosbruger, Timothy L.
AU - Duggal, Priya
AU - Goedert, James J.
AU - Kirk, Gregory D.
AU - Hoots, W. Keith
AU - Tobler, Leslie H.
AU - Busch, Michael
AU - Peters, Marion G.
AU - Rosen, Hugo R.
AU - Thomas, David L.
AU - Thio, Chloe L.
N1 - Funding Information:
Financial support: National Institutes of Health (NIH; grants R01-DA13324, R01-HL076902, R01-HD41224, R01-DA0334, R01-DA12568, UO1-HD-32632, UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590); National Cancer Institute (contract N02-CP-91027 with RTI International). The study was also funded in part by the Intramural Research Program, NIH.
PY - 2010/5/1
Y1 - 2010/5/1
N2 - Human genetic variation is a determinant of recovery from acute hepatitis C virus (HCV) infection; however, to date, single-nucleotide polymorphisms (SNPs) in only a limited number of genes have been studied with respect to HCV clearance. We determined whether SNPs in 112 selected immune response genes are important for HCV clearance, by genotyping 1536 SNPs in a cohort of 343 persons with natural HCV clearance and 547 persons with HCV persistence. PLINK (version 1.05) and Haploview (version 4.1) software packages were used to perform association, permutation, and haplotype analyses stratified by African American and European American race. Of the 1536 SNPs tested, 1426 (92.8%) were successfully genotyped. In African Americans, we identified 18 SNPs located in 11 gene regions that were associated with HCV infection outcome (empirical P value, < .01). In European Americans, there were 20 SNPs located in 8 gene regions associated with HCV infection outcome. Four of the gene regions studied (TNFSF18, TANK, HAVCR1, and IL18BP) contained SNPs for which the empirical P value was <.01 in both of the race groups. In this large-scale analysis of 1426 genotyped SNPs in 112 candidate genes, we identified 4 gene regions that are likely candidates for a role in HCV clearance or persistence in both African Americans and European Americans.
AB - Human genetic variation is a determinant of recovery from acute hepatitis C virus (HCV) infection; however, to date, single-nucleotide polymorphisms (SNPs) in only a limited number of genes have been studied with respect to HCV clearance. We determined whether SNPs in 112 selected immune response genes are important for HCV clearance, by genotyping 1536 SNPs in a cohort of 343 persons with natural HCV clearance and 547 persons with HCV persistence. PLINK (version 1.05) and Haploview (version 4.1) software packages were used to perform association, permutation, and haplotype analyses stratified by African American and European American race. Of the 1536 SNPs tested, 1426 (92.8%) were successfully genotyped. In African Americans, we identified 18 SNPs located in 11 gene regions that were associated with HCV infection outcome (empirical P value, < .01). In European Americans, there were 20 SNPs located in 8 gene regions associated with HCV infection outcome. Four of the gene regions studied (TNFSF18, TANK, HAVCR1, and IL18BP) contained SNPs for which the empirical P value was <.01 in both of the race groups. In this large-scale analysis of 1426 genotyped SNPs in 112 candidate genes, we identified 4 gene regions that are likely candidates for a role in HCV clearance or persistence in both African Americans and European Americans.
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U2 - 10.1086/651606
DO - 10.1086/651606
M3 - Article
C2 - 20331378
AN - SCOPUS:77950945422
SN - 0022-1899
VL - 201
SP - 1371
EP - 1380
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 9
ER -