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慢性肝病中的鳞状细胞癌抗原-1(SERPINB3)多态性

Squamous cell carcinoma antigen-1 (SERPINB3) polymorphism in chronic liver disease.

作者信息

Turato C, Ruvoletto M G, Biasiolo A, Quarta S, Tono N, Bernardinello E, Beneduce L, Fassina G, Cavalletto L, Chemello L, Merkel C, Gatta A, Pontisso P

机构信息

Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy.

出版信息

Dig Liver Dis. 2009 Mar;41(3):212-6. doi: 10.1016/j.dld.2008.06.001. Epub 2008 Jul 25.

Abstract

BACKGROUND

The serpin squamous cell carcinoma antigen (SCCA, SERPINB3) has been found over-expressed in primary liver cancer and at lower extent in cirrhosis and chronic hepatitis. A novel SCCA-1 variant (SCCA-PD), presenting a single mutation in the reactive centre (Gly351Ala), has been recently identified (rs3180227).

AIM

To explore SCCA-1 polymorphism in patients with HCV infection as single etiologic factor and different extent of liver disease.

METHODS

One hundred and fourty-eight patients with chronic HCV infection (45 chronic hepatitis, 53 cirrhosis, 50 HCC) and 50 controls were evaluated. SCCA-1 polymorphism was studied by restriction fragment length polymorphism and confirmed randomly by direct sequencing. Circulating SCCA-IgM complex was determined by ELISA.

RESULTS

SCCA-PD was detected with higher frequency in cirrhotic patients (45.3%, odds ratio=2.62; 95%CI 1.13-6.10, p=0.038) than in patients with chronic hepatitis or in controls (24.4% and 24%, respectively). Intermediate figures were found in hepatocarcinoma (36.0%). SCCA-IgM in serum was lower in patients carrying SCCA-PD than in wild type patients and the difference was statistically significant in cirrhotic patients (mean+/-S.D.=117.45+/-54.45 U/ml vs. 268.52+/-341.27 U/ml, p=0.026).

CONCLUSIONS

The newly identified SCCA-PD variant was more frequently found in liver cirrhosis, suggesting that patients carrying this polymorphism are more prone to develop progressive liver fibrosis.

摘要

背景

丝氨酸蛋白酶抑制剂鳞状细胞癌抗原(SCCA,SERPINB3)已被发现在原发性肝癌中过度表达,在肝硬化和慢性肝炎中表达程度较低。最近已鉴定出一种新的SCCA-1变体(SCCA-PD),其反应中心存在单一突变(Gly351Ala)(rs3180227)。

目的

探讨丙型肝炎病毒(HCV)感染作为单一病因因素且患有不同程度肝病的患者中SCCA-1多态性。

方法

对148例慢性HCV感染患者(45例慢性肝炎、53例肝硬化、50例肝癌)和50例对照进行评估。通过限制性片段长度多态性研究SCCA-1多态性,并通过直接测序随机确认。采用酶联免疫吸附测定法测定循环SCCA-IgM复合物。

结果

肝硬化患者中检测到SCCA-PD的频率(45.3%,优势比=2.62;95%可信区间1.13-6.10,p=0.038)高于慢性肝炎患者或对照(分别为24.4%和24%)。肝癌患者中该比例处于中间水平(36.0%)。携带SCCA-PD的患者血清中的SCCA-IgM低于野生型患者,且在肝硬化患者中差异具有统计学意义(均值±标准差=117.45±54.45 U/ml对268.52±341.27 U/ml,p=0.026)。

结论

新鉴定的SCCA-PD变体在肝硬化中更频繁出现,表明携带这种多态性的患者更容易发生进行性肝纤维化。

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