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

Abstract

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

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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