The Correlation between Single Nucleotide Polymorphism of MBOAT7 and PNPLA3 Genes to The Degree of Hepatic Fibrosis in HCV Patients: An Experience from Egypt

S. Youssef, E. Abbas, Yasser Hamada Ahmed Aly, S. Seif
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Abstract

Objectives: To detect the correlation between the single nucleotide polymorphisms (SNPs) in MBOAT7 and PNPLA3 genes and hepatic fibrosis in hepatitis C virus (HCV) Egyptian patients, and to highlight the additive effect, if any, of MBOAT7 on the correlation of PNPLA3 polymorphism with liver fibrosis in HCV patients from Egypt. Methods: In this cross-sectional study, we recruited treatment-naive patients with chronic HCV. The rs738409 (PNPLA3) and rs641738 (MBOAT7) polymorphisms were assessed by Real-Time PCR. We utilized the METAVIR‐Score to classify the degree of hepatic fibrosis and necroinflammatory activity. Results: A total of 93 patients (mean age 42.72 ± 10.46; males = 49.5%) were included. Our analysis showed that 10.8% of the patients had GG genotype of the PNPLA3 gene and 46.2% had TT genotype of the MBOAT7 gene.  Compared to combined CC and GC genotypes, carriers of GG genotype in PNPLA3 gene were more likely to be males (p =0.041), have higher fibrosis grade (p =0.043), have higher serum creatinine (p =0.036), higher TSH (p =0.017) and higher viral load (p =0.045). Notably, we found a significant association between TT genotype in MBOAT7 and advanced fibrosis only (but not with necroinflammation (p >0.05). Our multivariate analysis showed that the GG genotype in the PNPLA3 gene and TT genotype in the MBOAT7 gene were independent predictors of advanced fibrosis. Conclusion: PNPLA3 GG genotype and MBOAT7 TT genotype are independent predictors for hepatic fibrosis, and thus might be linked to faster disease progression.
MBOAT7和PNPLA3基因单核苷酸多态性与HCV患者肝纤维化程度的相关性:来自埃及的经验
目的:检测MBOAT7和PNPLA3基因单核苷酸多态性(snp)与埃及丙型肝炎病毒(HCV)患者肝纤维化之间的相关性,并强调MBOAT7对PNPLA3多态性与埃及HCV患者肝纤维化相关性的加性作用(如果有的话)。方法:在这项横断面研究中,我们招募了未接受治疗的慢性HCV患者。采用Real-Time PCR检测rs738409 (PNPLA3)和rs641738 (MBOAT7)多态性。我们使用METAVIR‐Score对肝纤维化程度和坏死炎症活性进行分类。结果:共93例患者(平均年龄42.72±10.46;男性= 49.5%)。我们的分析显示10.8%的患者为PNPLA3基因GG型,46.2%的患者为MBOAT7基因TT型。与CC和GC联合基因型相比,PNPLA3基因GG基因型携带者多为男性(p =0.041),纤维化程度高(p =0.043),血清肌酐(p =0.036)、TSH (p =0.017)和病毒载量高(p =0.045)。值得注意的是,我们发现MBOAT7的TT基因型仅与晚期纤维化(但与坏死性炎症无关)有显著相关性(p < 0.05)。我们的多变量分析显示PNPLA3基因中的GG基因型和MBOAT7基因中的TT基因型是晚期纤维化的独立预测因子。结论:PNPLA3 GG基因型和MBOAT7 TT基因型是肝纤维化的独立预测因子,因此可能与更快的疾病进展有关。
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