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Host Genetic Factors and Vaccine-Induced Immunity to HBV Infection: Haplotype Analysis
Journal article   Open access   Peer reviewed

Host Genetic Factors and Vaccine-Induced Immunity to HBV Infection: Haplotype Analysis

Kelli K Ryckman, Katherine Fielding, Adrian V Hill, Maimuna Mendy, Pura Rayco-Solon, Giorgio Sirugo, Marianne A van der Sande, Pauline Waight, Hilton C Whittle, Andrew J Hall, …
PloS one, Vol.5(8), pp.e12273-e12273
2010
DOI: 10.1371/journal.pone.0012273
PMCID: PMC2923624
PMID: 20806065
url
https://doi.org/10.1371/journal.pone.0012273View
Published (Version of record) Open Access

Abstract

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 = 9.1×10 −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.
Genetics and Genomics Genetics of Disease Genetics of the Immune System

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