慢性乙型肝炎患者降钙素基因相关肽和α-干扰素-λ4基因多态性对α-干扰素治疗应答的影响*

doi:10.3969/j.issn.1672-5069.2022.06.007

摘要/Abstract

摘要： 目的探讨慢性乙型肝炎(CHB)患者血清降钙素基因相关肽(CGRP)和α-干扰素-λ4(IFNL4)基因多态性对α-干扰素治疗应答的影响。方法 2018年9月～2021年2月我院诊治的CHB患者92例,给予所有患者α-干扰素α-2b治疗1年。采用聚合酶链反应-限制性片段长度多态性检测血CGRP基因rs155209位点及IFNL4基因rs368234815和rs12979860位点多态性,应用Logistic回归分析基因多态性与α-干扰素治疗应答的关系。结果在治疗1年末,本组应答67例(72.8%),未获得完全应答25例(27.2%);非应答组CGRP-rs155209位点CC基因型和等位基因C比率分别为36.0%和56.0%,显著高于应答组的16.4%和32.8%(P＜0.05);非应答组IFNL4-rs368234815位点TT/TT基因型和TT基因频率分别为76.0%和86.0%,显著低于应答组的92.5%和95.5%(P＜0.05);非应答组IFNL4-rs12979860位点CC、CT和TT基因型比率分别为44.0%、44.0%和12.0%,与应答组的40.3%、46.3%和13.4%比,无显著性差异(P＞0.05);应用非条件Logistic回归模型计算校正性别和年龄,结果显示CGRP-rs155209位点CC基因型是影响治疗无应答的危险基因型【OR值为1.489(95%CI:1.103～2.009)】,而IFNL4-rs368234815位点TT/TT 基因型是α-干扰素治疗应答的保护基因型【OR值为0.652(95%CI:0.477～0.893)】。结论 CGRP基因rs155209位点CC基因型是接受α-干扰素治疗CHB患者可能无应答的危险基因型,而IFNL4基因rs368234815 位点TT/TT 基因型可能是治疗应答的保护基因型,将影响CHB患者对α-干扰素治疗的生化和病毒学应答反应。

关键词: 慢性乙型肝炎, α-干扰素, 降钙素基因相关肽, α-干扰素-λ4, 基因多态性, 应答

Abstract: Objective The aim of this study was to explore the correlation of polymorphisms of calcitonin gene-related peptide (CGRP) and interferon-λ4 (IFNL4) genes to response toα-interferon therapy in patients with chronic hepatitis B (CHB). Methods A total of 92 patients with CHB were enrolled in our hospital between September 2018 and February 2021, and all were treated with α-interferon for 1 year. The polymorphisms of CGRP gene at rs155209 locus, and IFNL4 gene at rs368234815 and rs12979860 loci were detected by polymerase chain reaction-restriction fragment length polymorphism. The Logistic regression analysis was applied to reveal the correlation of polymorphisms of genes to response of antiviral therapy. Results At the end of 1-year antiviral therapy, the complete response (CR) was obtained in 67 cases(72.8%) anddidn’t obtained in 25 cases (27.2%); the proportions of CC genotype and C allele at CGRP-rs155209 locus in patients without CR were 36.0% and 56.0%, significantly higher than 16.4% and 32.8% in patients who got CR (P<0.05); the frequencies of TT/TT genotype and TT gene at IFNL4-rs368234815 locus in non-response patients were 76.0% and 86.0%, significantly lower than 92.5% and 95.5% (P<0.05) in responded ones; the proportions of CC, CT and TT genotypes at IFNL4-rs12979860 loci in non-response patients were 44.0%, 44.0% and 12.0%, not significantly different compared with 40.3%, 46.3% and 13.4% (P>0.05) in responded ones; the unconditional Logistic regression analysis with corrected gender and age showed that CC genotype at CGRP-rs155209 locus was a risk genotype for poor response to α-interferon therapy [OR=1.489 (95%CI: 1.103-2.009)], while TT/TT genotype at IFNL4-rs368234815 locus was a protective genotype [OR=0.652 (95%CI: 0.477-0.893)]. Conclusion The CC genotype at CGRP-rs155209 locus is a risk genotype for poor response to α-interferon therapy in patients with chronic hepatitis B, while the TT/TT genotype at IFNL4-rs368234815 locus is a protective one, which both might impact the biochemical and virological responses to α-interferon therapy, and needs further investigation.

Key words: Hepatitis B, α-interferon, Calcitonin gene-related peptide, interferon-λ4, Gene polymorphism, Response

齐孝安, 卢金喜, 袁林. 慢性乙型肝炎患者降钙素基因相关肽和α-干扰素-λ4基因多态性对α-干扰素治疗应答的影响^*[J]. 实用肝脏病杂志, 2022, 25(6): 784-787.

Qi Xiaoan, Lu Jinxi, Yuan Lin. Correlation of polymorphisms of calcitonin gene-related peptide and α-interferon-λ4 genes to response to α-interferon therapy in patients with chronic hepatitis B[J]. Journal of Practical Hepatology, 2022, 25(6): 784-787.

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慢性乙型肝炎患者降钙素基因相关肽和α-干扰素-λ4基因多态性对α-干扰素治疗应答的影响^*

Correlation of polymorphisms of calcitonin gene-related peptide and α-interferon-λ4 genes to response to α-interferon therapy in patients with chronic hepatitis B

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