Raquel Francine Liermann Garcia, Simone Moreira, Leslie Ecker Ferreira, Christian Evangelista Garcia, Mauro de Souza Leite Pinho, Paulo Henrique Condeixa de França, Departamento de Medicina, Universidade da Região de Joinville/Univille, Joinville, 89219-719 Santa Catarina, Brazil.
World J Gastroenterol. 2013 Nov 14;19(42):7399-404. doi: 10.3748/wjg.v19.i42.7399.
To analyze the role of rs12979860 and rs8099917 polymorphisms in hepatitis C virus (HCV) genotype 1 infection of Brazilians.
A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C (CHC) who had completed a 48-wk regimen of pegylated-interferon α-2a or -2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and 199 healthy blood donors (controls) from a single site between January 2010 and January 2012. Data on the patients' response to treatment was collected. Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin (IL)28B gene fragment encompassing the single nucleotide polymorphisms (SNPs) rs12979860 (C/T) and rs8099917 (T/G) was carried out for 79 of the CHC patients and 199 of the controls. Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients.
SNP rs12979860 genotyping was successful in 99.5% of the controls and 97.2% of the CHC patients, whereas the SNP rs8099917 genotyping was successful in 95.5% of the controls and 100% of the CHC patients. The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups, with significantly higher genotype frequencies of CC and TT in the controls (P = 0.037 and 0.046, respectively) and of TT and GG in the CHC patients (P = 0.0009 and 0.0001, respectively). Analysis of the CHC patients who achieved sustained virological response (SVR) to treatment (n = 55) indicated that the rs12979860 C allele and CC genotype were predictors of SVR (P = 0.02). No significant correlation was found between rs8099917 genotypes and treatment response, but carriers of the T allele showed significantly higher rates of SVR (P = 0.02). Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917 (P = 0.07).
The higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCV-infected individuals may indicate a potential protective role for these IL28B-related polymorphisms.
分析 rs12979860 和 rs8099917 多态性在巴西丙型肝炎病毒（HCV）基因型 1 感染中的作用。
2010 年 1 月至 2012 年 1 月，从六个大城市医疗中心招募了 145 名接受过聚乙二醇干扰素 α-2a 或 -2b 联合利巴韦林治疗 48 周的慢性丙型肝炎基因型 1（CHC）成年患者（病例组），并招募了来自一个单一地点的 199 名健康献血者（对照组）。收集了患者对治疗的反应数据。对 79 例 CHC 患者和 199 例对照组进行了白细胞介素（IL）28B 基因片段内包含单核苷酸多态性（SNP）rs12979860（C/T）和 rs8099917（T/G）的 IL28B 基因的聚合酶链反应-限制性片段长度多态性基因分型。对其余 66 例 CHC 患者进行了这两个 SNP 的双向扩增子测序。
对照组和 CHC 患者的 SNP rs12979860 基因分型成功率分别为 99.5%和 97.2%，而 SNP rs8099917 基因分型成功率分别为 95.5%和 100%。对照组和 CHC 患者组的 rs12979860 和 rs8099917 基因型和等位基因分布均存在显著差异，对照组的 CC 和 TT 基因型频率显著较高（P=0.037 和 0.046），CHC 患者的 TT 和 GG 基因型频率显著较高（P=0.0009 和 0.0001）。对治疗后获得持续病毒学应答（SVR）的 CHC 患者（n=55）进行分析，结果表明 rs12979860 C 等位基因和 CC 基因型是 SVR 的预测因子（P=0.02）。未发现 rs8099917 基因型与治疗反应之间存在显著相关性，但 T 等位基因携带者的 SVR 率显著较高（P=0.02）。对获得 SVR 的患者进行连锁不平衡分析显示，rs12979860 和 rs8099917 之间存在显著关联（P=0.07）。
未感染 HCV 的个体中 rs12979860 C 等位基因和 rs8099917 T 等位基因的频率较高，这可能表明这些与 IL28B 相关的多态性具有潜在的保护作用。
