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日本年轻成年人群中细胞因子基因单核苷酸多态性对乙型肝炎疫苗接种后抗-HBs抗体产生的影响。

Influence of single nucleotide polymorphisms of cytokine genes on anti-HBs antibody production after hepatitis B vaccination in a Japanese young adult population.

作者信息

Yukimasa Nobuyasu, Sato Shoichi, Oboshi Wataru, Watanabe Toru, Uzawa Ryuichi

机构信息

Graduate School of Health Sciences, Kagawa Prefectural University of Health Sciences.

出版信息

J Med Invest. 2016;63(3-4):256-61. doi: 10.2152/jmi.63.256.

Abstract

Hepatitis B (HB) vaccination is one of the most efficient tools to prevent the transmission of the virus. Considerable variability exists in HB vaccine responses, with 5-10% of healthy Japanese adults demonstrating no response following a standard vaccination. Recently, polymorphisms of immune-regulatory genes, such as cytokine genes, have been reported to influence the immune response to HB vaccine. The aim of this study was to investigate the underlying mechanisms of the genetic association between several cytokine gene polymorphisms and the immune response to HB vaccination in a Japanese population. One hundred and twenty three vaccinated young adults were classified according to the level of antibody-titer (anti-HBs). Single nucleotide polymorphism typing for IFN-γ (+874, 3'-UTR), IL-10 (-591, -819, -1082), and TNF-α (-308, -857), was accomplished using the PCR-RFLP or SSP-PCR method. The TNF-α (-857) CC type and the IL-10 (-1082) AG type were present more frequently in the low titer group than in the high titer group. The TNF-α (-857) CC type was found to be significantly associated with low response of serum anti-HBs. The anti-HBs antibody was not readily produced in the IL-10 (-1082) AG and TNF-α (-857) CC haplotype. Conversely, the antibody was readily produced in the IL-10 (-1082) AA and TNF-α (-857) CC haplotype, and the IL-10 (-1082) AA and TNF-α (-857) CT haplotype, suggesting a high likelihood of the IL-10 (-1082) AG type to be included in the low anti-HBs group, and high anti-HBs antibody production in those with the TNF-α (-857) CT type. These SNPs may produce ethnically-specific differences in the immune response to HB vaccine in the Japanese population. J. Med. Invest. 63: 256-261, August, 2016.

摘要

乙型肝炎(HB)疫苗接种是预防该病毒传播最有效的手段之一。HB疫苗接种反应存在相当大的变异性,5%至10%的健康日本成年人在标准接种后无反应。最近,有报道称免疫调节基因(如细胞因子基因)的多态性会影响对HB疫苗的免疫反应。本研究的目的是调查日本人群中几种细胞因子基因多态性与HB疫苗接种免疫反应之间遗传关联的潜在机制。123名接种疫苗的年轻成年人根据抗体滴度(抗-HBs)水平进行分类。使用PCR-RFLP或SSP-PCR方法完成了IFN-γ(+874,3'-UTR)、IL-10(-591、-819、-1082)和TNF-α(-308、-857)的单核苷酸多态性分型。低滴度组中TNF-α(-857)CC型和IL-10(-1082)AG型的出现频率高于高滴度组。发现TNF-α(-857)CC型与血清抗-HBs低反应显著相关。在IL-10(-1082)AG和TNF-α(-857)CC单倍型中不易产生抗-HBs抗体。相反,在IL-10(-1082)AA和TNF-α(-857)CC单倍型以及IL-10(-1082)AA和TNF-α(-857)CT单倍型中容易产生抗体,这表明IL-10(-1082)AG型很可能包含在抗-HBs低的组中,而TNF-α(-857)CT型的人抗-HBs抗体产生量高。这些单核苷酸多态性可能在日本人群对HB疫苗的免疫反应中产生种族特异性差异。《医学调查杂志》63:256 - 261,2016年8月。

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