Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda, Spain.
Servicio de Digestivo, Hospital Virgen de la Salud, 45004 Toledo, Spain.
Biomolecules. 2019 Apr 9;9(4):143. doi: 10.3390/biom9040143.
The Duffy antigen receptor for chemokines rs12075 polymorphism regulates leukocyte trafficking and proinflammatory chemokine homeostasis. Hepatitis C virus (HCV)-mediated liver fibrosis is associated with an uncontrolled inflammatory response. In this study, we evaluate the association between the rs12075 polymorphism and liver stiffness progression in HCV-infected patients. We carried out a retrospective cohort study (repeated measures design) in 208 noncirrhotic patients with chronic hepatitis C (CHC) who had at least two liver stiffness measurements (LSM) with a separation of at least 12 months. We used generalized linear models to analyze the association between rs12075 polymorphism and outcome variables. During a follow-up of 46.6 months, the percentage of patients with stages of fibrosis F0/F1 decreased ( < 0.001), while LSM values and the percentage of patients with cirrhosis increased ( < 0.001). This pattern of changes was maintained in each of the groups of patients analyzed according to their rs12075 genotypes (AA or AG/GG). However, the variations in liver stiffness characteristics were lower in patients with the rs12075 AG/GG genotype (AG/GG versus AA). Thereby, in the adjusted analysis, patients with the rs12075 AG/GG genotype had a lower risk of an increased value of LSM2/LSM1 arithmetic mean ratio (AMR = 0.83; = 0.001) and of an increase in LSM ≥ 5 kPa (odds ratio (OR) = 0.28; = 0.009). Besides, patients with rs12075 AG/GG had a lower risk of cirrhosis progression (OR = 0.24; = 0.009). No significant associations were found for an increase in LSM ≥ 10 kPa. We found an association between the rs12075 single nucleotide polymorphism (SNP) and CHC progression. Specifically, patients with the rs12075 AG/GG genotype had a lower risk of liver fibrosis progression and development of cirrhosis.
趋化因子受体 Duffy 对化学增敏素 rs12075 多态性调节白细胞迁移和前炎性趋化因子动态平衡。丙型肝炎病毒(HCV)介导的肝纤维化与失控的炎症反应有关。在这项研究中,我们评估了 rs12075 多态性与 HCV 感染患者肝硬度进展之间的关系。我们对 208 例非肝硬化慢性丙型肝炎(CHC)患者进行了回顾性队列研究(重复测量设计),这些患者至少有两次肝硬度测量(LSM),两次测量间隔至少 12 个月。我们使用广义线性模型分析 rs12075 多态性与结局变量之间的关系。在 46.6 个月的随访中,纤维化分期 F0/F1 的患者比例下降(<0.001),而 LSM 值和肝硬化患者的比例增加(<0.001)。根据 rs12075 基因型(AA 或 AG/GG)分析的每组患者均保持这种变化模式。然而,rs12075 AG/GG 基因型患者的肝硬度特征变化较低(AG/GG 与 AA)。因此,在调整分析中,rs12075 AG/GG 基因型患者的 LSM2/LSM1 算术平均值比(AMR=0.83;<0.001)增加和 LSM 增加≥5kPa 的风险较低(比值比(OR)=0.28;<0.001)。此外,rs12075 AG/GG 患者肝硬化进展的风险较低(OR=0.24;<0.009)。未发现 LSM 增加≥10kPa 与进展之间存在显著关联。我们发现 rs12075 单核苷酸多态性(SNP)与 CHC 进展之间存在关联。具体来说,rs12075 AG/GG 基因型患者的肝纤维化进展和肝硬化发展风险较低。