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Fas基因中-670A>G基因多态性与丙型肝炎慢性期血清标志物谷草转氨酶/血小板比值指数、谷草转氨酶/谷丙转氨酶与显著肝纤维化及肝硬化的相关性

Association of genetic polymorphism -670A>G in the Fas gene and serum markers AST platelet ratio index, AST/ALT with significant fibrosis and cirrhosis in chronic hepatitis C.

作者信息

Deghady Akram, Abdou Alaa, El-Neanaey Wafaa Ahmed, Diab Iman

机构信息

Department of Clinical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

出版信息

Genet Test Mol Biomarkers. 2012 Jun;16(6):531-5. doi: 10.1089/gtmb.2011.0098. Epub 2012 Feb 21.

DOI:10.1089/gtmb.2011.0098
PMID:22352690
Abstract

AIM

This study was carried out to evaluate the association of genetic polymorphism -670A>G in the promoter of Fas gene as well as serum biomarkers aspartate aminotransferase (AST) platelet ratio index (APRI) and AST/alanine aminotransferase (ALT) with significant fibrosis and cirrhosis in chronic hepatitis C patients. Seventy-nine patients with chronic hepatitis C in addition to 80 age- and sex-matched healthy controls were evaluated for genetic polymorphism -670A>G of Fas gene by polymerase chain reaction-restriction fragment length polymorphism and serum biomarkers APRI and AST/ALT in relation to significant fibrosis and cirrhosis diagnosed by liver biopsy.

RESULT

Genetic polymorphism -670A>G in Fas gene was associated with significant liver fibrosis and cirrhosis. Heterozygous mutation was found in 11.4% of patients and 10% of controls, while homozygous mutation was found only in 7.6% of patients. Odds ratio (OR) was statistically not significant (OR=1.93, 95% confidence interval=0.76-4.92). Mean values of APRI and AST/ALT were significantly higher in patients with (F3-F4) compared with those with (F0-F2). (p-value <0.001 for APRI and p=0.007 for AST/ALT). In addition, APRI showed a better sensitivity than AST/ALT for prediction of significant fibrosis.

CONCLUSION

Genetic polymorphism -670A>G of Fas gene was associated with significant fibrosis and cirrhosis in chronic hepatitis C patients. APRI and AST/ALT are independent predictors for significant fibrosis. APRI showed a better sensitivity than AST/ALT for prediction of significant fibrosis. Moreover, APRI can be used as an index to exclude liver cirrhosis without performing liver biopsy.

摘要

目的

开展本研究以评估Fas基因启动子区-670A>G基因多态性以及血清生物标志物天冬氨酸氨基转移酶(AST)与血小板比值指数(APRI)和AST/丙氨酸氨基转移酶(ALT)与慢性丙型肝炎患者显著肝纤维化和肝硬化的相关性。通过聚合酶链反应-限制性片段长度多态性方法对79例慢性丙型肝炎患者以及80例年龄和性别匹配的健康对照者进行Fas基因-670A>G基因多态性评估,并检测血清生物标志物APRI和AST/ALT,同时通过肝活检诊断显著肝纤维化和肝硬化。

结果

Fas基因-670A>G基因多态性与显著肝纤维化和肝硬化相关。11.4%的患者和10%的对照者存在杂合突变,而仅7.6%的患者存在纯合突变。优势比(OR)无统计学意义(OR=1.93,95%置信区间=0.76-4.92)。与F0-F2期患者相比,F3-F4期患者的APRI和AST/ALT平均值显著更高(APRI的p值<0.001,AST/ALT的p=0.007)。此外,APRI在预测显著肝纤维化方面的敏感性高于AST/ALT。

结论

Fas基因-670A>G基因多态性与慢性丙型肝炎患者的显著肝纤维化和肝硬化相关。APRI和AST/ALT是显著肝纤维化的独立预测指标。APRI在预测显著肝纤维化方面的敏感性高于AST/ALT。此外,APRI可作为一种指标,在不进行肝活检的情况下排除肝硬化。

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