A single nucleotide polymorphism of the low molecular mass polypeptide 7 gene influences the interferon response in patients with chronic hepatitis C
A single nucleotide polymorphism of the low molecular mass polypeptide 7 gene influences the interferon response in patients with chronic hepatitis C
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DOI：
10.1046/j.1365-2893.2002.00365.x
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发表时间：
2002-09
影响因子：
2.5
通讯作者：
Y. Sugimoto;N. Kuzushita;T. Takehara;T. Kanto;T. Tatsumi;T. Miyagi;M. Jinushi;K. Ohkawa;M. Horimoto;A. Kasahara;M. Hori;Y. Sasaki;N. Hayashi
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文献类型：
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作者：
Y. Sugimoto;N. Kuzushita;T. Takehara;T. Kanto;T. Tatsumi;T. Miyagi;M. Jinushi;K. Ohkawa;M. Horimoto;A. Kasahara;M. Hori;Y. Sasaki;N. Hayashi
概括。与抗原加工相关的转运蛋白 (TAP) 和低分子量多肽 (LMP) 在人类白细胞抗原 (HLA) I 类限制性抗原呈递系统中发挥着至关重要的作用。本研究旨在阐明这些抗原呈递基因多态性是否会影响慢性丙型肝炎患者对干扰素（IFN）治疗的反应。通过聚合酶链反应限制性片段长度多态性测定了175名丙型肝炎病毒（HCV）患者的TAP和LMP基因多态性。对持续应答者 (n=49) 和无应答者 (n=126) 之间这些基因的频率进行了比较，并根据对 IFN 的生化和病毒学反应进行分类。 TAP1*、TAP2* 和 LMP2 基因在持续缓解者和无缓解者之间的分布没有差异。然而，持续缓解者中的 LMP7-K 基因频率高于无缓解者[比值比 2.3（95% 置信区间 1.1-4.6）； 16% vs 7.9%]。多变量分析显示，LMP7-K和HCV-RNA数量是影响IFN治疗结果的独立因素[4.5（1.4-14）； P=0.011、0.40（0.24-0.65）； P=0.0003，分别]。此外，在低病毒载量（≤ 2.0 Meq/mL）的患者中，与无 LMP7-K 的患者相比，LMP7-K 阳性患者的持续缓解率更高 [5.9 (1.6-22)； 82% vs 44%； P=0.0062]。这些结果表明，LMP7基因的单核苷酸多态性是独立影响慢性丙型肝炎患者对IFN反应的重要宿主因素之一。
summary. Transporter associated with antigen processing (TAP) and low molecular mass polypeptides (LMP) play crucial roles in the human leukocyte antigen (HLA) class I‐restricted antigen presenting systems. This study was performed to elucidate whether these antigen‐presenting gene polymorphisms could influence the response to interferon (IFN) treatment in patients with chronic hepatitis C. Polymorphisms of TAP and LMP genes in 175 hepatitis C virus (HCV) patients were determined by polymerase chain reaction‐restriction fragment length polymorphism. The frequencies of these genes were compared between sustained‐responders (n=49) and nonresponders (n=126), classified by biochemical and virological responses to IFN. The distributions of TAP1*, TAP2*, and LMP2 genes between sustained‐responders and nonresponders did not differ. However, LMP7‐K gene frequency in sustained‐responders was higher than that in nonresponders [odds ratio 2.3 (95% confidence interval 1.1–4.6); 16%vs 7.9%]. Multivariate analysis revealed that LMP7‐K and HCV‐RNA quantity were independent factors influencing the outcome of IFN therapy [4.5 (1.4–14); P=0.011, 0.40 (0.24–0.65); P=0.0003, respectively]. Furthermore, among patients with a low viral load (≤ 2.0 Meq/mL), the LMP7‐K positive patients had an even higher ratio of sustained response compared to those without LMP7‐K [5.9 (1.6–22); 82%vs 44%; P=0.0062]. These findings suggest that a single nucleotide polymorphism of LMP7 gene is one of the important host factors which independently influence the response to IFN in patients with chronic hepatitis C.