TY - JOUR
T1 - Hepatitis C hypervariable region 1
T2 - Association of reduced selection pressure in African Americans with treatment failure
AU - Park, Vicki M.
AU - Mason, Barbara C.
AU - Krushkal, Julia
AU - Li, Rongling
AU - Riely, Caroline
AU - Fleckenstein, Jaquelyn
N1 - Funding Information:
Acknowledgments This work was supported by NIAID U19 AI-48216 and UTHSC GCRC M01 RR-00211. The authors thank Anne Madey for her excellent work as study coordinator. Kathy Kenwright, Amy Miller, and Swapna Menon are acknowledged gratefully for their contributions to the project. We thank Drs. M. Nei and S. Kumar for their advice regarding the MEGA Z-test for selection. Sequencing was performed at the Molecular Resource Center of the University of Tennessee Health Science Center.
PY - 2007/10
Y1 - 2007/10
N2 - In a prospective therapeutic trial, features of the hepatitis C quasispecies were investigated as possible markers of therapeutic response. Individuals chronically infected with hepatitis C genotype 1 received antiviral therapy consisting of α-interferon plus ribavirin. The study targeted the most rapidly evolving segment of the viral genome, hypervariable region 1 within the envelope-2 gene. Among individuals failing to clear virus in response to therapy, significant differences were observed between quasispecies of African-American and Caucasian subjects. While distance measures for synonymous substitutions were similar between racial subgroups, measures of distance at the amino acid level (nonsynonymous substitutions) varied significantly. Taken together, the observed patterns of variability corresponded to reduced host selection pressure against hypervariable region 1 in African-American nonresponders. Reduced selection pressure was present at baseline and persisted through treatment and follow-up, suggesting population stratification of host factors that influence selection pressure on hepatitis C virus.
AB - In a prospective therapeutic trial, features of the hepatitis C quasispecies were investigated as possible markers of therapeutic response. Individuals chronically infected with hepatitis C genotype 1 received antiviral therapy consisting of α-interferon plus ribavirin. The study targeted the most rapidly evolving segment of the viral genome, hypervariable region 1 within the envelope-2 gene. Among individuals failing to clear virus in response to therapy, significant differences were observed between quasispecies of African-American and Caucasian subjects. While distance measures for synonymous substitutions were similar between racial subgroups, measures of distance at the amino acid level (nonsynonymous substitutions) varied significantly. Taken together, the observed patterns of variability corresponded to reduced host selection pressure against hypervariable region 1 in African-American nonresponders. Reduced selection pressure was present at baseline and persisted through treatment and follow-up, suggesting population stratification of host factors that influence selection pressure on hepatitis C virus.
KW - African American
KW - Caucasian
KW - Hepatitis C
KW - Hypervariable region 1
KW - Nonsynonymous substitution
KW - Selection pressure
UR - http://www.scopus.com/inward/record.url?scp=34548503608&partnerID=8YFLogxK
U2 - 10.1007/s10620-006-9726-8
DO - 10.1007/s10620-006-9726-8
M3 - Article
C2 - 17410445
AN - SCOPUS:34548503608
SN - 0163-2116
VL - 52
SP - 2540
EP - 2549
JO - Digestive diseases and sciences
JF - Digestive diseases and sciences
IS - 10
ER -