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肝脂肪变性与 HCV 基因 1 型感染患者 MTP 基因-493G/T 多态性的关系。

Association between hepatic steatosis and MTP gene -493G/T polymorphism in the patients with HCV genotype 1 infection.

机构信息

Çukurova University, Faculty of Medicine, Department of Gastroenterology, Adana, Turkey.

Çukurova University, Faculty of Medicine, Department of Gastroenterology, Adana, Turkey.

出版信息

Infect Genet Evol. 2019 Jun;70:101-106. doi: 10.1016/j.meegid.2019.02.019. Epub 2019 Feb 18.

Abstract

AIM

Hepatitis C virus (HCV) affects approximately 250 million people worldwide. If patients are untreated, 80% of patients with chronic HCV develop liver failure, liver cirrhosis (LC), and hepatocellular carcinoma (HCC). HCV genotype 1 is the most prevalent among the infected individuals with HCV. Hepatic steatosis is known as accumulation of lipid molecules in hepatocytes, and its prevalence is approximately 55% in CHC infection. The reason of HCV-related hepatic steatosis in CHC infection is mainly HCV core protein. HCV core protein inhibits activities of microsomal triglyceride transfer protein (MTP) which is a lipid transfer protein expressed in the liver. The -493G/T polymorphism in the promoter region of MTP gene has been associated with HCV-related hepatic steatosis. This polymorphism in MTP gene influences MTP mRNA expression, therefore which might also affect lipid transfer. We evaluated the association between MTP gene polymorphism and the risk of HCV genotype 1-related hepatic steatosis.

METHODS

In the current study, MTP gene polymorphism was explored in 144 biopsy-proven chronic HCV genotype 1 patients by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

RESULTS

The results showed that there were no any difference between the steatosis and the non-steatosis groups for the allele and genotype frequencies of the -493G/T polymorphism (P > .05). Moreover, MTP genotypes (GG vs. TG + TT) were not associated with BMI, fibrosis stages and the levels of biochemical parameters. Additionally, there were statistically significant differences in the biochemical parameters including triglyceride, total cholesterol, LDL, VLDL levels between the two groups (P < .05).

CONCLUSIONS

In conclusion, the current study demonstrates for the first time that MTP gene -493G/T polymorphism has not a major effect on the risk of HCV genotype 1-related hepatic steatosis in Turkish population. Further studies are imperative to clarify the association of this polymorphism with HCV genotype 1 infection in HCV-related hepatic steatosis.

摘要

目的

丙型肝炎病毒(HCV)影响全球约 2.5 亿人。如果未经治疗,80%的慢性 HCV 患者会发展为肝功能衰竭、肝硬化(LC)和肝细胞癌(HCC)。HCV 基因型 1 在 HCV 感染者中最为常见。肝脂肪变性是指肝细胞内脂质分子的积累,在 CHC 感染中其患病率约为 55%。HCV 相关肝脂肪变性的原因主要是 HCV 核心蛋白。HCV 核心蛋白抑制了在肝脏中表达的脂质转移蛋白微粒体甘油三酯转移蛋白(MTP)的活性。MTP 基因启动子区域的-493G/T 多态性与 HCV 相关肝脂肪变性有关。该 MTP 基因多态性影响 MTP mRNA 表达,因此可能也会影响脂质转移。我们评估了 MTP 基因多态性与 HCV 基因型 1 相关肝脂肪变性风险之间的关系。

方法

在本研究中,通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,对 144 例经肝活检证实的慢性 HCV 基因型 1 患者的 MTP 基因多态性进行了研究。

结果

结果显示,脂肪变性组和非脂肪变性组在-493G/T 多态性的等位基因和基因型频率方面没有差异(P>0.05)。此外,MTP 基因型(GG 与 TG+TT)与 BMI、纤维化分期和生化参数水平无关。此外,两组间生化参数(甘油三酯、总胆固醇、LDL、VLDL 水平)有统计学差异(P<0.05)。

结论

总之,本研究首次表明,在土耳其人群中,MTP 基因-493G/T 多态性对 HCV 基因型 1 相关肝脂肪变性的风险没有主要影响。进一步的研究对于阐明该多态性与 HCV 基因型 1 感染在 HCV 相关肝脂肪变性中的关系至关重要。

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