台湾乙型肝炎 e 抗原阳性母亲所生儿童乙型肝炎疫苗接种失败与 NTCP 基因变异的关系。

Genetic variants of NTCP gene and hepatitis B vaccine failure in Taiwanese children of hepatitis B e antigen positive mothers.

机构信息

Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.

Division of Pediatric Gastroenterology, Department of Pediatrics, Liver Research Center, Chang Gung Memorial Hospital, Linkou Branch, and Chang Gung University College of Medicine, Taoyuan, Taiwan.

出版信息

Hepatol Int. 2022 Aug;16(4):789-798. doi: 10.1007/s12072-022-10350-7. Epub 2022 May 30.

DOI:10.1007/s12072-022-10350-7

PMID:35635688

Abstract

BACKGROUND AND AIMS

Hepatitis B virus (HBV) vaccine failure remains a hurdle to the global elimination of HBV infections in the vaccination era. We aimed to elucidate the relationships between HBV entry receptor sodium taurocholate co-transporting polypeptide (NTCP) and vaccine failure in children born to highly infectious mothers.

METHODS

The genetic variants rs7154439, rs4646285, rs4646287, and rs2296651 were genotyped in 170 children with chronic HBV infections and 138 control children of mothers positive for hepatitis B e antigen (HBeAg). All children received hepatitis B immunoglobulin and complete HBV vaccination. Total RNAs from 82 adult non-tumor liver tissues were quantified for NTCP, type I interferons and interferon-induced transmembrane protein 3 (IFITM3) levels.

RESULTS

A higher rate of the GA/AA genotype (28.3% vs. 15.3%, p = 0.006) of the genetic variant rs4646287 in intron 1 of the NTCP gene was detected in control children compared to the carrier children. The rs4646287 G > A genotype was associated with younger ages at which spontaneous HBeAg seroconversion occurred (10.8 ± 8.4 vs. 14.6 ± 8.7 years, p = 0.003) in chronic HBV-infected children. Unique correlation patterns of NTCP and innate immunity-related genes (type I interferons and IFITM3) were found in HBV-infected liver tissues with the rs4646287 G > A genotype.

CONCLUSION

The rs4646287 G > A genotype of the NTCP gene may be associated with lower risk for HBV vaccine failure in children born to highly infectious mothers. The protective effect of rs4646287 G > A was also present in carrier children, evidenced by earlier spontaneous HBeAg seroconversion.

摘要

背景与目的

乙型肝炎病毒 (HBV) 疫苗失效仍然是在接种疫苗时代全球消除 HBV 感染的一个障碍。我们旨在阐明在高传染性母亲所生的儿童中，HBV 进入受体牛磺胆酸钠共转运蛋白 (NTCP) 与疫苗失效之间的关系。

方法

对 170 名慢性 HBV 感染儿童和 138 名 HBeAg 阳性母亲的对照儿童进行了 NTCP 基因的 rs7154439、rs4646285、rs4646287 和 rs2296651 基因多态性的基因分型。所有儿童均接受乙型肝炎免疫球蛋白和完整的 HBV 疫苗接种。定量检测 82 例成人非肿瘤肝组织中 NTCP、I 型干扰素和干扰素诱导跨膜蛋白 3 (IFITM3) 的总 RNA 水平。

结果

与携带儿童相比，对照组儿童 NTCP 基因内含子 1 的 rs4646287 遗传变异的 GA/AA 基因型（28.3%对 15.3%，p=0.006）的发生率更高。rs4646287 G>A 基因型与慢性 HBV 感染儿童自发 HBeAg 血清学转换的年龄更小有关（10.8±8.4 岁对 14.6±8.7 岁，p=0.003）。在 rs4646287 G>A 基因型的 HBV 感染肝组织中发现了 NTCP 和固有免疫相关基因（I 型干扰素和 IFITM3）的独特相关模式。