Department of Internal Medicine III, Medical University, Vienna, Austria.
J Hepatol. 2013 Nov;59(5):964-71. doi: 10.1016/j.jhep.2013.06.030. Epub 2013 Jul 10.
BACKGROUND & AIMS: Single nucleotide polymorphisms (SNPs) in the inosine triphosphate pyrophosphatase (ITPA) gene protect patients from ribavirin induced anemia. To investigate other possible protective cofactors, gender differences were analyzed in patients with HCV genotype 1.
Hemoglobin levels at baseline (Hb0) and the decline after 4 weeks of treatment (HbΔ4) were analyzed in 308 chronic hepatitis C patients participating in 5 Austrian trials (n=308, age 43.9 ± 11.1, male:185, female:123, BMI 25.3 ± 3.9, no cirrhosis: n=259, liver cirrhosis: n=49). All patients were treated with 180 μg peginterferon-alpha 2a and ribavirin [1000-1200 mg/d; females: mean (95% CI) 15.8 mg/kg (15.4-16.2); males 14.3 (14.1-14.5); p<0.001]. The SNPs rs6051702, rs1127354, rs7270101 and IL28B rs12979860 were analyzed by the StepOnePlus Real time PCR System.
188 were major alleles homozygotes; 95 (30.8%) carried the minor allele (C) of rs6051702, 47 (15.3%) of rs1127354 (A), and 69 (22.4%) of rs7270101 (C). The overall Hb0 was 14.8 g/dl (14.6-14.9) [mean (95%CI); females 13.7 (13.5-13.9); males 15.5; 15.3-15.6; p<0.001]. The overall HbΔ4 was greater in major allele homozygotes [2.8 g/dl (2.6-3.0)] than in minor allele carriers [1.6 (1.4-1.9); p<0.001]. Irrespective of the ITPA genotypes HbΔ4 was smaller in female [2.0 (1.7-2.2)] than in male patients [2.6 (2.4-2.8); p<0.001] and among females in premenopausal [1.5 (1.3-1.8)] than in postmenopausal patients [2.7 (2.3-3.1); p<0.001].
Irrespective of the protective effect of ITPA mutations, premenopausal females less likely develop ribavirin induced anemia.
肌苷三磷酸焦磷酸酶（ITPA）基因中的单核苷酸多态性（SNPs）可保护患者免受利巴韦林引起的贫血。为了研究其他可能的保护性协同因子，本研究分析了 HCV 基因型 1 患者的性别差异。
对 308 例参加 5 项奥地利试验的慢性丙型肝炎患者（n=308，年龄 43.9±11.1 岁，男性 185 例，女性 123 例，BMI 25.3±3.9，无肝硬化 n=259 例，肝硬化 n=49 例）的基线血红蛋白水平（Hb0）和治疗 4 周后的下降值（HbΔ4）进行分析。所有患者均接受 180μg 聚乙二醇干扰素-α2a 和利巴韦林[1000-1200mg/d；女性：平均（95%CI）15.8mg/kg（15.4-16.2）；男性 14.3（14.1-14.5）；p<0.001]治疗。通过 StepOnePlus 实时 PCR 系统分析 rs6051702、rs1127354、rs7270101 和 IL28B rs12979860 的 SNP。
188 例为主要等位基因纯合子；95 例（30.8%）携带 rs6051702 的次要等位基因（C），47 例（15.3%）携带 rs1127354（A），69 例（22.4%）携带 rs7270101（C）。总体 Hb0 为 14.8g/dl（14.6-14.9）[平均值（95%CI）；女性 13.7（13.5-13.9）；男性 15.5；15.3-15.6；p<0.001]。主要等位基因纯合子的总体 HbΔ4 较大[2.8g/dl（2.6-3.0）]，而次要等位基因携带者较小[1.6（1.4-1.9）；p<0.001]。无论 ITPA 基因型如何，女性的 HbΔ4[2.0（1.7-2.2）]均小于男性患者[2.6（2.4-2.8）；p<0.001]，且绝经前女性[1.5（1.3-1.8）]小于绝经后女性[2.7（2.3-3.1）；p<0.001]。
无论 ITPA 突变的保护作用如何，绝经前女性发生利巴韦林诱导性贫血的可能性较低。
