Liu Shuyuan, Cao Danfeng, Shen Yunsong, Li Yalin, Li Ying, Shi Li, Yu Jiankun, Li Chuanyin, Zhang Xinwen, Sun Mingbo, Yao Yufeng
Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Disease, Kunming 650118, China.
The First People's Hospital in Yunnan Province & The Affiliated Hospital of Kunming Science and Technology University, Kunming 650032, China.
Hum Immunol. 2017 Nov;78(11-12):731-738. doi: 10.1016/j.humimm.2017.10.005. Epub 2017 Oct 13.
Endoplasmic reticulum aminopeptidases (ERAPs), ERAP1 and ERAP2, are critical components in the antigen-presentation system and are specialized to produce optimal-sized peptides for HLA I binding. ERAP gene polymorphisms have been correlated with HLA-associated diseases. To investigate the association between ERAP gene polymorphisms and HCV chronic infection, a TaqMan assay was used to genotype 4 SNPs (rs27044, rs30187, rs26618 and rs26653) in ERAP1 and 2 SNPs (rs2248374 and rs2549782) in ERAP2 genes in 376 Chinese Han HCV chronic infections and 324 healthy Chinese Han controls. The allelic distribution of rs26618 in the ERAP1 gene and rs2248374 in ERAP2 gene were both significantly different in case and control groups. The C-allele of rs26618 had an increased HCV chronicity risk compared with the T-allele (P=.025, OR=1.318, 95%CI: 1.035-1.677), and the same effect was found in A-allele of rs2248374 compared with G-allele (P=0.046, OR=1.244, 95%CI: 1.004-1.540). There were notable differences in the genotype distribution in analysis using the dominant genetic model in rs26618 (CC+CT vs. TT; P=0.007, OR=1.473, 95%CI: 1.091-1.989) and recessive genetic model in rs2248374 (AA vs. AG+GG; P=0.003, OR=1.548, 95%CI: 1.026-2.335). In addition, rs26618 and rs2248374-genotype combination played noteable effects on the clinical parameters. These results indicated that the ERAP gene may play a critical role in HCV chronicity in this Chinese Han population.
内质网氨基肽酶(ERAPs),即ERAP1和ERAP2,是抗原呈递系统的关键组成部分,专门用于产生适合与HLA I结合的最佳大小的肽段。ERAP基因多态性与HLA相关疾病有关。为了研究ERAP基因多态性与HCV慢性感染之间的关联,采用TaqMan检测法对376例中国汉族HCV慢性感染者和324例健康中国汉族对照者的ERAP1基因中的4个单核苷酸多态性(SNP,rs27044、rs30187、rs26618和rs26653)以及ERAP2基因中的2个SNP(rs2248374和rs2549782)进行基因分型。ERAP1基因中的rs26618和ERAP2基因中的rs2248374的等位基因分布在病例组和对照组中均存在显著差异。与T等位基因相比,rs26618的C等位基因增加了HCV慢性感染的风险(P = 0.025,比值比[OR]=1.318,95%置信区间[CI]:1.035 - 1.677),与G等位基因相比,rs2248374的A等位基因也有同样的作用(P = 0.046,OR = 1.244,95%CI:1.004 - 1.540)。在使用显性遗传模型分析rs26618(CC + CT与TT;P = 0.007,OR = 1.473,95%CI:1.091 - 1.989)和隐性遗传模型分析rs2248374(AA与AG + GG;P = 0.003,OR = 1.548,95%CI:1.026 - 2.335)时,基因型分布存在显著差异。此外,rs26618和rs2248374的基因型组合对临床参数有显著影响。这些结果表明,ERAP基因可能在该中国汉族人群的HCV慢性感染中起关键作用。