310例中国人基因组干扰素α1/α2基因多态性研究

doi:10.3969/j.issn.1672-5069.2021.01.005

摘要/Abstract

摘要： 目的若药品α-干扰素亚型与人体体内基因型不一致,接受抗病毒治疗的患者可被诱导产生更多的抗干扰素中和抗体,导致不应答和治疗失败。通过分析中国人群干扰素α1(IFNA1)和α2(IFNA2)基因多态性,可帮助阐明重组人干扰素α1和α2在中国人群中的遗传背景,为临床用药提供参考。方法在单核苷酸多态性数据库中分别检索IFNA1基因和IFNA2基因编码区错义突变单核苷酸多态性(SNP)位点,再在千人基因组数据库查询收录的中国人IFNA1和IFNA2等位基因的分布情况,分析两种基因多态性并计算出相关的等位基因频率。结果在千人基因组数据库共收录310例中国人双倍染色体基因组序列,所有中国人均有IFNA1和IFNA2基因座,其中,IFNA1基因座含有IFNα1、IFNα1(Ala137Val)和IFNα1(Arg148Gln) 三种等位基因,基因频率分别为99.6%、0.2%和0.2%;IFNA2基因座也含有IFNα2b、IFNα2b(Leu140Val)和IFNα2b(Ala120Thr)三种等位基因,基因频率分别为98.4%、0.2%和1.4%。结论 IFNα1和IFNα2b分别是中国人群IFNA1和IFNA2基因座的优势等位基因,在我国批准上市的IFNα1b、IFNα2a和IFNα2b三种亚型α-干扰素中,仅有IFNα2b与中国人基因型一致。

关键词: 病毒性肝炎, α-干扰素, 等位基因, 基因多态性

Abstract: Objective If it is not consistent with the genotype in a given patient, the recombinant human interferon alpha would induce the production of more anti-interferon neutralization antibodies and leads to therapeutic failure. By analyzing the gene polymorphisms of IFNA1 and IFNA2 in Chinese population, the genetic background of recombinant human interferon α1 and α2 in Chinese population was clarified, so as to provide a reference for clinical medication. Methods Single nucleotide polymorphism (SNP) loci in the coding region of IFNA1 and IFNA2 were retrieved from the SNP database, and the distribution of IFNA1 and IFNA2 alleles in Chinese population were searched in the 1000 genome database. The polymorphisms of the two genes were counted and all of allele frequencies were calculated. Results A total of 310 Chinese diploid genome sequences were included in the 1000 genomes database, and all the Chinese persons had IFNA1 and IFNA2 gene loci; the IFNα1 gene loci contained IFNα1,IFNA1(Ala137Val) and IFNα1(Arg148Gln) alleles, with the gene frequencies of 99.6%, 0.2% and 0.2%, respectively; the IFNA2 gene locus also contained three alleles: e.g. IFNα2b, IFNα2b (Leu140Val) and IFNα2b (Ala120Thr), with the gene frequencies of 98.4%, 0.2%, and 1.4%, respectively.Conclusion The IFNα1 and IFNα2b are the dominant alleles of IFNA1 and IFNA2 gene loci in Chinese population, while only IFNα2b is consistent with the Chinese human genotype among the three subtypes of IFNα1b, IFNα2a and IFNα2 approved for marketing in China.

Key words: Viral hepatitis, Interferon alpha;Allele gene;Gene polymorphism

王兵, 盛海, 卢晨, 程联胜, 龚庆国. 310例中国人基因组干扰素α1/α2基因多态性研究[J]. 实用肝脏病杂志, 2021, 24(1): 14-18.

Wang Bing, Sheng Hai, Lu Chen, et al. Gene polymorphism of interferon α1 and α2 in 310 Chinese person’s genomes[J]. Journal of Practical Hepatology, 2021, 24(1): 14-18.

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