Altintas Zuhal, Altintas Engin
Medical Genetics, Faculty of Medicine, Mersin University, Mersin, TUR.
Gastroenterology and Hepatology, Faculty of Medicine, Mersin University, Mersin, TUR.
Cureus. 2025 Apr 13;17(4):e82213. doi: 10.7759/cureus.82213. eCollection 2025 Apr.
Background Organic anion-transporting polypeptides (OATPs) are responsible for the cellular uptake of a broad range of endogenous compounds and xenobiotics in multiple tissues. The aim of our study was to determine whether variations in OATP1B1 and OATP1B3 affect the side effects experienced by hepatitis C patients treated with direct-acting antivirals (DAAs). Methods This study included 199 hepatitis C patients treated with DAAs. Ledipasvir/sofosbuvir or ombitasvir/paritaprevir/ritonavir ± dasabuvir and 162 control individuals without hepatitis C. Treatment-related side effects were recorded. The OATP1B1 gene variations c.388A>G and c.521T>C and the OATP1B3 gene variations c.334T>G and c.699G>A were analyzed via the polymerase chain reaction-restriction fragment length polymorphism method. Allele/genotype combinations of OATP1B1 and OATP1B3 haplotypes were evaluated. Results Side effects were observed in 53 (26.6%) of 199 hepatitis C patients. There were skin mucosal lesions in 19 patients (36%), fatigue in 18 patients (34%), pruritus in 11 patients (20.5%), and other in five patients (9.5%). There was a significant relationship between the c.334T>G variant and side effects (p = 0.030). The frequency distribution of the c.334T>G variant was in Hardy-Weinberg equilibrium. The frequencies of the patient group and the control group were 65.3% and 63%, respectively. We found a significant difference between the patient and control groups in terms of the haplotype ratios of c.388A>G and c.521T>C (p = 0.036). Conclusions We found a significant relationship between the c.334T>G variant in OATP1B3 and DAA-related side effects in hepatitis C patients.
背景 有机阴离子转运多肽(OATPs)负责多种组织中多种内源性化合物和外源性物质的细胞摄取。我们研究的目的是确定OATP1B1和OATP1B3的变异是否会影响接受直接作用抗病毒药物(DAAs)治疗的丙型肝炎患者所经历的副作用。方法 本研究纳入了199例接受DAAs治疗的丙型肝炎患者。来迪派韦/索磷布韦或奥比他韦/帕利瑞韦/利托那韦±达沙布韦,以及162例无丙型肝炎的对照个体。记录与治疗相关的副作用。通过聚合酶链反应-限制性片段长度多态性方法分析OATP1B1基因变异c.388A>G和c.521T>C以及OATP1B3基因变异c.334T>G和c.699G>A。评估OATP1B1和OATP1B3单倍型的等位基因/基因型组合。结果 199例丙型肝炎患者中有53例(26.6%)出现了副作用。19例患者(36%)出现皮肤黏膜病变,18例患者(34%)出现疲劳,11例患者(20.5%)出现瘙痒,5例患者(9.5%)出现其他症状。c.334T>G变异与副作用之间存在显著相关性(p = 0.030)。c.334T>G变异的频率分布符合哈迪-温伯格平衡。患者组和对照组的频率分别为65.3%和63%。我们发现患者组和对照组在c.388A>G和c.521T>C单倍型比例方面存在显著差异(p = 0.036)。结论 我们发现OATP1B3中的c.334T>G变异与丙型肝炎患者中与DAAs相关的副作用之间存在显著相关性。