Laboratorio de Investigacao Medica em Hepatologia por Virus (LIM-47), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Departamento de Molestias Infecciosas e Parasitarias, Faculdade de Medicina, Universidade de Sao Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255. Bairro Cerqueira Cesar. Sao Paulo, SP, Brazil. CEP 05403-000.
Pathog Dis. 2021 Mar 20;79(3). doi: 10.1093/femspd/ftab007.
Several factors are associated with the progression of chronic hepatitis C: comorbidities, lifestyle, and pathogenic factors, including immune response, apoptosis and heredity. Single nucleotide polymorphisms (SNPs) in the PNPLA3 and TM6SF2 genes are more widely studied genetic risk factors, while CXCL9-11 chemokines produced by hepatocytes in the process of infection are less well studied. Our aim was to evaluate the influence of CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 in liver fibrosis when analysed together with PNPLA3 rs738409 and TM6SF2 rs58542926. The study included 219 patients with chronic hepatitis C. SNP genotyping was performed by real-time PCR. Univariate and multivariate analyses were used to detect the association between SNPs and advanced fibrosis in a recessive genetic model. All SNPs had a minimum allele frequency >5%, and CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 were in high linkage disequilibrium (D' ≥ 0.84). In the multivariate analysis, we observed that male gender (P = 0.000), older age (P = 0.025), moderate to intense inflammatory activity (P = 0.002), moderate to accentuated hepatic steatosis (P = 0.026) and the CT genotype of the TM6SF2 rs58542926 SNP (P = 0.014) presented significant associations with advanced fibrosis. Overall, the CXCL9 rs10336, CXCL10 rs3921, CXCL11 rs4619915 and PNPLA3 rs738409 SNPs did not influence liver fibrosis among patients with chronic hepatitis C.
合并症、生活方式和发病因素，包括免疫反应、细胞凋亡和遗传因素。PNPLA3 和 TM6SF2 基因中的单核苷酸多态性（SNP）是更为广泛研究的遗传风险因素，而感染过程中肝细胞产生的 CXCL9-11 趋化因子研究较少。我们的目的是评估 CXCL9 rs10336、CXCL10 rs3921 和 CXCL11 rs4619915 在与 PNPLA3 rs738409 和 TM6SF2 rs58542926 一起分析时对肝纤维化的影响。该研究纳入了 219 例慢性丙型肝炎患者。采用实时 PCR 进行 SNP 基因分型。采用单变量和多变量分析检测 SNP 与隐性遗传模型中晚期纤维化之间的关系。所有 SNP 的最小等位基因频率均>5%，且 CXCL9 rs10336、CXCL10 rs3921 和 CXCL11 rs4619915 高度连锁不平衡（D'≥0.84）。在多变量分析中，我们观察到男性（P=0.000）、年龄较大（P=0.025）、中重度炎症活动（P=0.002）、中重度肝脂肪变性（P=0.026）和 TM6SF2 rs58542926 SNP 的 CT 基因型（P=0.014）与晚期纤维化显著相关。总体而言，CXCL9 rs10336、CXCL10 rs3921、CXCL11 rs4619915 和 PNPLA3 rs738409 SNP 并未影响慢性丙型肝炎患者的肝纤维化。
