HLA and cytokine gene polymorphisms are independently associated with responses to hepatitis B vaccination

Wang, Chengbin; Tang, Jianming; Song, Wei; Lobashevsky, Elena; Wilson, Craig M.; Kaslow, Richard A.

doi:10.1002/hep.20142

Cited by 172 publications

(129 citation statements)

References 57 publications

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“…After applying a permutation test for correction for multiple testing seven SNPs maintained their statistical significance (Table 2). Consistent with previous reports, 21 we detected a strong genetic association between host response to hepatitis B vaccine and the MHC locus on chromosome 6 (rs5000563, most significant combined P-value ¼ 5.6 Â 10 -10 ; OR (95%CI) ¼ 0.60 (0.52-0.71)). Up to 11 polymorphisms within this region, spanning over 1.3 Mb, showed significant association in the second stage.…”

Section: Resultssupporting

confidence: 92%

“…Several reports have associated genetic variability in the HLA locus with host response to hepatitis B vaccine in different populations. [21][22][23] Consistent with those studies, we detected a strong genetic association with the HLA region in the current Indonesian population sample. Out of 64 genotyped SNPs within the HLA region, 16 showed nominally significant P-values in the first stage (Supplementary Table S1).…”

Section: Discussionsupporting

confidence: 91%

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New genetic associations detected in a host response study to hepatitis B vaccine

et al. 2010

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The immune response to hepatitis B vaccination differs greatly among individuals, with 5-10% of healthy people failing to produce protective levels of antibodies. Several factors have been implicated in determining this response, chiefly individual genetic variation and age. Aiming to identify genes involved in the response to hepatitis B vaccination, a two-stage investigation of 6091 single-nucleotide polymorphisms (SNPs) in 914 immune genes was performed in an Indonesian cohort of 981 individuals showing normal levels of anti-HBs versus 665 individuals displaying undetectable levels of anti-HBs 18 months after initial dose of the vaccine. Of 275 SNPs identified in the first stage (476 normal/372 nonresponders) with Po0.05, significant associations were replicated for 25 polymorphisms in 15 genes (503 normal/295 nonresponders). We validated previous findings (HLA-DRA, rs5000563, P-value combined ¼ 5.57 Â 10 À10 ; OR (95%CI) ¼ 0.61 (0.52-0.71)). In addition, we detected a new association outside of the human leukocyte antigen loci region that passed correction for multiple testing. This SNP is in the 3 0 downstream region of FOXP1, a transcription factor involved in B-cell development (P-value combined ¼ 9.2 Â 10 À6 ; OR (95%CI) ¼ 1.38 (1.2-1.6)).These findings might help to understand the biological reasons behind vaccine failure and other aspects of variation in the immune responses of healthy individuals.

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Section: Resultssupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

New genetic associations detected in a host response study to hepatitis B vaccine

et al. 2010

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“…Briefly, it appears that alleles associated with high/normal response are: DRB1*01, DRB1*I1, DRB1*15, DQB1*0501, DPB1*0401 and DRPB1*0402; whereas alleles correlated with non-or poor response are: DRB1*03, DRB1*07, DQB1*02, DPB1*1101, DRB1*14, and DRQB1*020. The only HLA population-based study in individuals of African origin (other than the above twin study in Gambians) is that by Wang and colleagues who assessed vaccine-response genetics in an ethnically mixed US population comprising a large proportion of African-Americans (Wang et al, 2004). Non-response to vaccination was attributed to variants HLA-Cw*03, DRB1*07 and DQB1*02, whereas response was associated with DRB1*15 and DQB1*06 (all results adjusted for ethnicity and other covariates).…”

Section: Genetics Of Immunity Induced By Hbv Vaccinationmentioning

confidence: 99%

“…None of these are based on populations of native African origin. Wang and colleagues (Wang et al, 2004) studied a population of predominantly black African Americans and reported on a haplotype consisting of three IL4 SNPs (-1098G/T, rs2243248; -590C/T, rs2243250; and -33C/T, rs2070874) associated with good response to HBV vaccination, whereas those carrying a 4bp deletion in the IL12B promoter were shown to be non-responsive. In this sample HIV infection was also correlated with non-response to vaccination.…”

Section: Genetics Of Immunity Induced By Hbv Vaccinationmentioning

confidence: 99%

Host genetic factors in hepatitis B infection, liver cancer and vaccination response: A review with a focus on Africa

Hennig

Hall

2012

Science of The Total Environment

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The disease burden due to hepatitis B virus (HBV) infection remains significant; 350 million people are infected world-wide, and around half a million deaths each year are due to HBVrelated liver disease and hepatocellular carcinoma (HCC). Infant immunisation against infection was introduced in the early 1980s, the vaccine is routinely administered across regions where the disease is endemic and has been shown to be safe and effective. However, the large number of older individuals with persistent infection means that disease will not be reduced significantly for several decades. Furthermore, failure to respond to the vaccination has been observed in about 5% of vaccinees and to date we have limited information on the durability of vaccine protection against infection. Hepatitis B infection and disease pathogenesis are known to be influenced by a number of factors including host genetics factors. This review aims to give an overview of the role of genetic variation in persistent HBV infection and the development of liver disease including HCC. Vaccine-induced immunity is, at least in part, heritable and we also discuss findings on the genetic control of responses to HBV vaccination. The epidemiology of HBV infection differs by world region, as does the genetic makeup of individuals originating from different regions. This review focuses on the situation in Africa, where hepatitis B is highly endemic.

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“…Polymorphic variants in HLA genes have been found to be associated or linked with AR to hepatitis B vaccine (Kruskall et al 1992), influenza vaccine (Gelder et al 2002;Poland et al 2008a), measles vaccine (Poland 1998;Poland et al 2008b), and BCG tuberculosis vaccine (van Eden et al 1983), among others. However, non-MHC or non-HLA genes-IL1B, IL4R, IL6, IL10 and TNF-have also been found to be independently associated with response to hepatitis B vaccine (Wang et al 2004). Interestingly, although measles, mumps and rubella vaccines are all attenuated live vaccines that are administered simultaneously, the responses induced by these vaccines are influenced differently by host genetics (Kimman et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Genetic determinants of immune-response to a polysaccharide vaccine for typhoid

Majumder

Staats

Sarkar-Roy

et al. 2009

HUGO J

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Differences in immunological response among vaccine recipients are determined both by their genetic differences and environmental factors. Knowledge of genetic determinants of immunological response to a vaccine can be used to design a vaccine that circumvents immunogenetic restrictions. The currently available vaccine for typhoid is a pure polysaccharide vaccine, immune response to which is T-cell independent. Little is known about whether genetic variation among vaccinees associates with variation in their antibody response to a polysaccharide vaccine. We conducted a study on 1,000 individuals resident in an area at high-risk for typhoid; vaccinated them with the typhoid vaccine, measured their antibody response to the vaccine, assayed [2,000 curated SNPs chosen from 283 genes that are known to participate in immune-response; and analyzed these data using a strategy to (a) minimize the statistical problems associated with testing of multiple hypotheses, and (b) internally cross-validate inferences, using a half-sample design, with little loss of statistical power. The first stage analysis, using the first half-sample, identified 54 SNPs in 43 genes to be significantly associated with immune response. In the second-stage, these inferences were cross-validated using the second half-sample. First-stage results of only 8 SNPs (out of 54) in 7 genes (out of 43) were cross-validated. We tested additional SNPs in these 7 genes, and found 8 more SNPs to be significantly associated. Haplotypes constructed with these SNPs in these 7 genes also showed significant association. These 7 genes are DEFB1, TLR1, IL1RL1, CTLA4, MAPK8, CD86 and IL17D. The overall picture that has emerged from this study is that (a) immune response to polysaccharide antigens is qualitatively different from that to protein antigens, and (b) polymorphisms in genes involved in polysaccharide recognition, signal transduction, inhibition of T-cell proliferation, pro-inflammatory signaling and eventual production of antimicrobial peptides are associated with antibody response to the polysaccharide vaccine for typhoid.

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HLA and cytokine gene polymorphisms are independently associated with responses to hepatitis B vaccination

Abstract: Variable immune responses to hepatitis B virus (HBV) infection and recombinant HBV

Cited by 172 publications

References 57 publications

New genetic associations detected in a host response study to hepatitis B vaccine

New genetic associations detected in a host response study to hepatitis B vaccine

Host genetic factors in hepatitis B infection, liver cancer and vaccination response: A review with a focus on Africa

Genetic determinants of immune-response to a polysaccharide vaccine for typhoid

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