慢性丙型肝炎和慢性乙型肝炎患者ITPA基因多态性与聚乙二醇干扰素抗病毒治疗所致血小板减少症相关性分析

肝脏 ›› 2023, Vol. 28 ›› Issue (1): 95-99.

慢性丙型肝炎和慢性乙型肝炎患者ITPA基因多态性与聚乙二醇干扰素抗病毒治疗所致血小板减少症相关性分析

邓浩辉, 楼燕, 李晓强, 邱玖香

510000 广东广州医科大学附属市八医院感染病中心(邓浩辉,楼燕,李晓强),检验科(邱玖香)

收稿日期:2022-01-04 出版日期:2023-01-31 发布日期:2023-02-21
通讯作者: 邱玖香,Email:gz8hqjx@126.com
基金资助:
广东省医学科学技术研究基金项目(B2021302)

The relationship between single nucleotide polymorphisms of ITPA gene and thrombocytopenia induced by pegylated interferon therapy in chronic hepatitis C and chronic hepatitis B patients

DENG Hao-hui¹, LOU Yan¹, LI Xiao-qiang¹, QIU Jiu-xiang²

1. Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangdong 510060, China;
2. Department of Clinical Laboratory, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangdong 510060, China

Received:2022-01-04 Online:2023-01-31 Published:2023-02-21
Contact: QIU Jiu-xiang,Email:gz8hqjx@126.com

摘要/Abstract

摘要： 目的探讨慢性丙型肝炎(CHC)和慢性乙型肝炎(CHB)患者肌苷三磷酸酶(ITPA)基因多态性性(SNP)与聚乙二醇干扰素(Peg-IFN α-2b或α-2a)抗病毒治疗所致血小板减少症的相关性。方法纳入广州医科大学附属市八医院感染病中心2011年1月—2016年12月期间92例CHC和87例CHB患者,纳入的患者均使用Peg-IFN α-2a或α-2b抗病毒治疗并有48周完整的随访数据,采用直接测序法检测患者ITPA基因rs1127354位点SNP,并收集抗病毒治疗后第4、8、12、24、36和48周血小板变化,以及药物剂量调整情况的相关数据,使用SPSS 13.0软件进行统计分析。结果本研究纳入的92例CHC患者中,rs1127354位点CC型55例(59.8%),AC型31例(33.7%),AA型6例(6.5%);纳入的87例CHB患者中,rs1127354位点CC型53例(60.9%),AC型29例(33.3%),AA型5例(5.7%)。在CHC患者中,rs1127354位点AA/AC型在Peg-IFN/利巴韦林(RBV)治疗后4周(F=6.195, P=0.015)和8周(F=4.304, P=0.042)血小板下降水平显著高于CC型的患者,但在CHB患者中,rs1127354位点SNP与Peg-IFN抗病毒治疗后各时间点血小板下降水平无显著相关性(P>0.05)。CHC rs1127354位点AA/AC型的患者使用Peg-IFN/RBV抗病毒治疗过程中Peg-IFN剂量调整的构成比显著高于CC型的患者(χ2=4.796, P=0.029),但CHB rs1127354位点SNP与Peg-IFN剂量调整无显著相关性(χ²=0.051, P=0.822)。结论 CHC患者ITPA基因rs1127354位点SNP与Peg-IFN/RBV抗病毒治疗所致血小板减少症显著相关,但CHB患者ITPA基因rs1127354位点SNP与Peg-IFN抗病毒治疗所致血小板减少症无显著相关性。

关键词: 慢性乙型肝炎, 慢性丙型肝炎, 聚乙二醇干扰素, 基因多态性, 血小板减少症

Abstract: Objective To investigate the relationship between single nucleotide polymorphisms (SNP) of inosine triphosphatase (ITPA) gene and thrombocytopenia induced by pegylated interferon (Peg-IFN) therapy in chronic hepatitis C (CHC) and chronic hepatitis B patients (CHB). Methods A total of 92 CHC and 87 CHB patients treated by Peg-IFN α-2a or α-2b for 48 week (w) with complete clinical data collected from January 2011 to December 2016 were enrolled in this study. The SNPs of ITPA gene on rs1127354 site were detected by Sanger sequencing methods. The clinical data (platelets counts and dose adjustments of Peg-IFN) between patients with different SNPs on rs1127354 site at 4w, 8w, 12w, 24w, 36w and 48w after antiviral therapy were compared and analyzed using SPSS 13.0 software. Results Among the 92 CHC patients enrolled in this study, the genotypes of rs1127354 in 55 patients (59.8%) were homozygous CC, 31 patients (33.7%) were heterozygous AC and 6 patients (7.6%) were homozygous AA; among the 87 CHB patients, the genotypes of rs1127354 in 53 patients (60.9%) were homozygous CC, 29 patients (33.3%) were heterozygous AC and 5 patients (5.7%) were homozygous AA. In CHC patients, thrombocytopenia in rs1127354 AA/AC genotypes was more frequent than CC genotype at 4w (F=6.195, P=0.015) and 8w (F=4.304, P=0.042) after Peg-IFN/ribavirin (RBV) therapy. However, the difference in thrombocytopenia was not found between CHB patients with rs1127354 AA/AC and CC SNPs at different time points post antiviral therapy (P>0.05). In addition, the chances of Peg-IFN dose reduction were significantly higher in CHC patients with rs1127354 AA/AC than those with CC SNPs (χ²=4.796, P=0.029), but there was no difference between CHB patients with rs1127354 CC and AA/AC SNPs (χ²=0.051, P=0.822).Conclusion Peg-IFN induced thrombocytopenia is related to the gene polymorphisms of ITPA rs1127354 in CHC patients received Peg-IFN/ RBV therapy, but not to those of CHB patients received Peg-IFN therapy.

Key words: Chronic hepatitis B, Chronic hepatitis C, Inosine triphosphatase, Pegylated interferon, Single nucleotide polymorphisms, Thrombocytopenia

邓浩辉, 楼燕, 李晓强, 邱玖香. 慢性丙型肝炎和慢性乙型肝炎患者ITPA基因多态性与聚乙二醇干扰素抗病毒治疗所致血小板减少症相关性分析[J]. 肝脏, 2023, 28(1): 95-99.

DENG Hao-hui, LOU Yan, LI Xiao-qiang, QIU Jiu-xiang. The relationship between single nucleotide polymorphisms of ITPA gene and thrombocytopenia induced by pegylated interferon therapy in chronic hepatitis C and chronic hepatitis B patients[J]. Chinese Hepatolgy, 2023, 28(1): 95-99.

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