Gerges Marian, Shora Hassan, Abd-Elhamid Nahla, Abdel-Kareem Alaa, El-Nimr Sahar, Badawy Ahmed, Sharaf Ahmed, Gerby Manal El, Metwally Wafaa
Medical Microbiology and Immunology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Molecular biology/ Biochemistry, Port-said University, Egypt.
Infez Med. 2024 Sep 1;32(3):381-391. doi: 10.53854/liim-3203-13. eCollection 2024.
Hepatitis C virus (HCV) is a major risk factor for chronic hepatitis and hepatocellular carcinoma (HCC). Nuclear factor kappa B (NF-κB) is a transcription factor that functions in health and disease. Genetic variants of the NF-κB gene can affect its function and are associated with chronic inflammatory changes and malignant transformation. This case-control study is aimed to determine the possible association between NF-κB genetic variants and different outcomes of HCV infection among Egyptian patients.
295 subjects were recruited with allocation of participants in the representative group according to results of serological and molecular tests. Patients in the case group (group A) were further divided into three subgroups; subgroup I, mild chronic HCV, subgroup II, cirrhosis, and subgroup III, HCC subgroups (59 for each subgroup), group B included participants who experienced spontaneous viral clearance (n=59). All were compared to matched healthy control subjects, Group C (n=59). All participants were genotyped for NF-κB polymorphisms, rs11820062 by TaqMan assay and rs28362491 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
Risk analysis indicated that subjects carrying the rs11820062 A genotype are more susceptible to HCV infection (OR: 3.1; 95%, CI= 1.4-6.9). Subjects carrying the rs28362491 insertion genotype are at more risk of progression to cirrhosis when compared to healthy-controls and patients with mild chronic HCV (OR:7.7; 95% CI=2.4-24.3 and OR:5.1, 95% CI= 1.7-15.7, respectively) and also are at more risk of developing HCC when compared to healthy controls (OR:2.6; 95% CI= 0.94-7.3).
Polymorphisms affecting NF-κB different genes would modulate HCV infection susceptibility and clinical disease progression among Egyptian patients.
丙型肝炎病毒(HCV)是慢性肝炎和肝细胞癌(HCC)的主要危险因素。核因子κB(NF-κB)是一种在健康和疾病中发挥作用的转录因子。NF-κB基因的遗传变异可影响其功能,并与慢性炎症变化和恶性转化相关。本病例对照研究旨在确定埃及患者中NF-κB基因变异与HCV感染不同结局之间的可能关联。
招募了295名受试者,并根据血清学和分子检测结果将参与者分配到代表组中。病例组(A组)患者进一步分为三个亚组;亚组I,轻度慢性HCV,亚组II,肝硬化,亚组III,HCC亚组(每个亚组59例),B组包括经历自发病毒清除的参与者(n = 59)。将所有这些与匹配的健康对照受试者C组(n = 59)进行比较。所有参与者均通过TaqMan分析对NF-κB多态性rs11820062进行基因分型,并通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对rs28362491进行基因分型。
风险分析表明,携带rs11820062 A基因型的受试者更容易感染HCV(比值比:3.1;95%,置信区间= 1.4 - 6.9)。与健康对照和轻度慢性HCV患者相比,携带rs28362491插入基因型的受试者进展为肝硬化的风险更高(比值比分别为:7.7;95%置信区间= 2.4 - 24.3和比值比:5.1,95%置信区间= 1.7 - 15.7),并且与健康对照相比,发生HCC的风险也更高(比值比:2.6;95%置信区间= 0.94 - 7.3)。
影响NF-κB不同基因的多态性会调节埃及患者中HCV感染的易感性和临床疾病进展。