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Médecine du travail du personnel hospitalier

Genetic polymorphisms of CXCR5 and CXCL13 are associated with non-responsiveness to the hepatitis B vaccine

Auteur     Zhaojun Duan
Auteur     Xiangmei Chen
Auteur     Zhenglun Liang
Auteur     Ying Zeng
Auteur     Fengcai Zhu
Auteur     Lu Long
Auteur     Malcolm A. McCrae
Auteur     Hui Zhuang
Auteur     Tao Shen
Auteur     Fengmin Lu
Volume     32
Numéro     41
Pages     5316-5322
Publication     Vaccine
ISSN     1873-2518
Date     Sep 15, 2014
Résumé     A cohort based study has been undertaken to investigate the possible association of genetic polymorphisms in genes functionally related to follicular T helper (TfH) cells with non-responsiveness to hepatitis B virus (HBV) vaccination. A total of 24 single nucleotide polymorphisms (SNPs) in 6 TfH related genes (CXCR5, ICOS, CXCL13, IL-21, BCL6 and CD40L) were investigated in 20 non-responders and 45 responders to HBV vaccination. Genetic association analysis revealed that three SNPs (rs497916, rs3922, rs676925) in CXCR5 and one SNP (rs355687) in CXCL13 were associated with hepatitis B vaccine efficacy. In addition, significantly unbalanced distributions of two haplotypes, defined by three SNPs (rs497916, rs3922, rs676925) within CXCR5, were also seen between non-responders and responders. Furthermore, we demonstrated that the rs3922 « GG » genotype was associated with higher levels of CXCR5 than the « AG » and « AA » genotype in a group of healthy volunteers. A dual luciferase report assay was used to confirm that the « G » allele in rs3922 may lead to higher gene expression than the « A » allele, implicating that rs3922 might be a functional SNP affecting CXCR5 expression. These results indicated that polymorphism associated changes in CXCR5 expression in TfH cells may be associated with non-responsiveness to hepatitis B vaccination.

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doi:10.1016/j.vaccine.2014.07.064

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