TY - JOUR
T1 - Host genetic factors and vaccine-induced immunity to HBV infection: haplotype analysis
AU - Ryckman, Kelli K
AU - Fielding, Katherine
AU - Hill, Adrian V
AU - Mendy, Maimuna
AU - Rayco-Solon, Pura
AU - Sirugo, Giorgio
AU - van der Sande, Marianne
AU - Waight, Pauline
AU - Whittle, Hilton C
AU - Hall, Andrew J
AU - Williams, Scott M
AU - Hennig, Branwen J
N1 - FTX; DOAJ; (CC BY 4.0)
PY - 2010
Y1 - 2010
N2 - Hepatitis B virus (HBV) infection remains a significant health burden world-wide, although vaccines help decrease this problem. We previously identified associations of single nucleotide polymorphisms in several candidate genes with vaccine-induced peak antibody level (anti-HBs), which is predictive of long-term vaccine efficacy and protection against infection and persistent carriage; here we report on a haplotype-based analysis. A total of 688 SNPs from 117 genes were examined for a two, three and four sliding window haplotype analysis in a Gambian cohort. Analysis was performed on 197 unrelated individuals, 454 individuals from 174 families, and the combined sample (N = 651). Global and individual haplotype association tests were carried out (adjusted for covariates), employing peak anti-HBs level as outcome. Five genes (CD44, CD58, CDC42, IL19 and IL1R1) had at least one significant haplotype in the unrelated or family analysis as well as the combined analysis. Previous single locus results were confirmed for CD44 (combined global p = 9.1x10(-5) for rs353644-rs353630-rs7937602) and CD58 (combined global p = 0.008 for rs1414275-rs11588376-rs1016140). Haplotypes in CDC42, IL19 and IL1R1 also associated with peak anti-HBs level. We have identified strong haplotype effects on HBV vaccine-induced antibody level in five genes, three of which, CDC42, IL19 and IL1R1, did not show evidence of association in a single SNP analyses and corroborated the majority of these effects in two datasets. The haplotype analysis identified associations with HBV vaccine-induced immunity in several new genes.
AB - Hepatitis B virus (HBV) infection remains a significant health burden world-wide, although vaccines help decrease this problem. We previously identified associations of single nucleotide polymorphisms in several candidate genes with vaccine-induced peak antibody level (anti-HBs), which is predictive of long-term vaccine efficacy and protection against infection and persistent carriage; here we report on a haplotype-based analysis. A total of 688 SNPs from 117 genes were examined for a two, three and four sliding window haplotype analysis in a Gambian cohort. Analysis was performed on 197 unrelated individuals, 454 individuals from 174 families, and the combined sample (N = 651). Global and individual haplotype association tests were carried out (adjusted for covariates), employing peak anti-HBs level as outcome. Five genes (CD44, CD58, CDC42, IL19 and IL1R1) had at least one significant haplotype in the unrelated or family analysis as well as the combined analysis. Previous single locus results were confirmed for CD44 (combined global p = 9.1x10(-5) for rs353644-rs353630-rs7937602) and CD58 (combined global p = 0.008 for rs1414275-rs11588376-rs1016140). Haplotypes in CDC42, IL19 and IL1R1 also associated with peak anti-HBs level. We have identified strong haplotype effects on HBV vaccine-induced antibody level in five genes, three of which, CDC42, IL19 and IL1R1, did not show evidence of association in a single SNP analyses and corroborated the majority of these effects in two datasets. The haplotype analysis identified associations with HBV vaccine-induced immunity in several new genes.
KW - Adolescent
KW - Antigens, CD/genetics
KW - Female
KW - Haplotypes
KW - Hepatitis B/genetics
KW - Humans
KW - Immunity
KW - Interleukins/genetics
KW - Male
KW - Polymorphism, Single Nucleotide
KW - Receptors, Interleukin-1 Type I/genetics
KW - Viral Vaccines/immunology
U2 - 10.1371/journal.pone.0012273
DO - 10.1371/journal.pone.0012273
M3 - A1: Web of Science-article
C2 - 20806065
SN - 1932-6203
VL - 5
JO - PLoS ONE
JF - PLoS ONE
IS - 8
M1 - e12273
ER -