Genetic Polymorphisms of the IFNLR1 Gene Correlate with HCV Infection and Biochemical Features of Chronic HCV Patients in Yunnan, China
Genetic Polymorphisms of the IFNLR1 Gene Correlate with HCV Infection and Biochemical Features of Chronic HCV Patients in Yunnan, China
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DOI：
10.1080/08820139.2019.1642914
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发表时间：
2020-05
影响因子：
2.8
通讯作者：
A. Zhang;Yiqian Wang;X. Xia;Yuzhu Song
中科院分区：
文献类型：
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作者：
A. Zhang;Yiqian Wang;X. Xia;Yuzhu Song
摘要丙型肝炎病毒感染可导致严重的肝病，但其致病机制尚不完全清楚。细胞因子在感染中起着关键作用，细胞因子基因的遗传多态性在感染性疾病中被广泛研究。IL-28B基因变异与丙型肝炎病毒感染、病毒清除及患者的生化特征有关，但对其受体(IFNLR1/IL10RB)的研究较少。在这项研究中，我们收集了395名慢性丙型肝炎患者和397名正常对照，以研究IFNLR1基因的遗传作用。对8个TagSNP进行了基因分型，构建了单倍型。Rs7532146基因CT(23.80%vs.17.13%)和TT型(75.19%vs.81.36%)基因频率在丙型肝炎患者中分别高于和低于对照组(P=0.022；P=0.039)。单倍型GGAATCTC(P=0.028)和AAAGCCCT(P=0.002)是丙型肝炎病毒感染的危险因素，而单倍型GAAATCTT(P=0.027)对丙型肝炎病毒感染起保护作用。此外，我们还发现携带rs4489498基因TT的丙型肝炎患者的ALT水平显著低于其他基因携带者(CC vs.TT：P=0.037；CT vs.TT：P=0.013)。携带rs4489498基因CC的丙型肝炎病毒载量最高(CC vs.CT：P=0.006；CC vs.TT：P=0.039)。综上所述，IFNLR1基因的基因分型和单倍型与中国人丙型肝炎病毒感染和生化特征有关。
ABSTRACT Hepatitis C virus (HCV) infection could lead to serious liver diseases, but the pathogenic mechanisms were not completely clear. Cytokines play critical roles in infection, and the genetic polymorphisms in the cytokine genes are widely studied in infectious diseases. The variations in the IL28B gene were associated with HCV infection, viral clearance, and biochemical features of patients, but the studies of its receptor (IFNLR1/IL10RB) were rare. In this study, we collected 395 chronic HCV patients and 397 normal controls to investigate the genetic role of the IFNLR1 gene. Eight tagSNPs were genotyped, and the haplotypes were constructed. Genotypes CT (23.80% vs. 17.13%) and TT (75.19% vs. 81.36%) of rs7532146 showed higher and lower frequencies in HCV patients than that in controls (P = .022; P = .039). Haplotypes GGAATCTC (P = .028) and AAAGCCCT (P = .002) were risk factors for HCV infection, but haplotype GAAATCTT (P = .027) played protective role in HCV infection. Moreover, we identified that the ALT level was significantly lower in HCV patients with genotype TT of rs4489498 than those with other genotypes (CC vs. TT: P = .037; CT vs. TT: P = .013). HCV viral load was highest in HCV patients with genotype CC of rs4489498 than in patients with other two genotypes (CC vs. CT: P = .006; CC vs. TT: P = .039). In conclusion, the genotypes and haplotypes in the IFNLR1 gene were associated with HCV infection and biochemical features of Chinese HCV patients.