OBJECTIVE α-fetoprotein (AFP) expression is activated during the embryonic stage or hepatocellular carcinogenesis, so it is presumed that AFP is a key endogenous molecule to promote cell proliferation or differentiation. We carried out gene screening in an unknown family with hyper-alpha-fetoproteinemia and some sporadic menopausal women, and discussed the relationship between AFP expression and liver cirrhosis. METHODS Peripheral blood samples from family members, patients with malignant liver tumors, and normal controls were collected. Full-length sequence of AFP was amplified and directly sequenced, and compared with normal controls. HNF-1α and HNF-1β in plasma levels of family members, patients with liver cancer, newborns, pregnant women, and normal subjects were detected by ELISA, and the relationship between HNF-1 and AFP mutation or high expression was evaluated. RESULTS There was a mutation in AFP promoter region at c.-200 C>T, which was located at the binding site of AFP hepatocyte nuclear factor 1 (HNF-1). AFP was higher than 4000 ng/L in all members carrying the mutation, but liver cancer was excluded in the family with hyper-alpha-fetoprotein. However, cirrhosis occurred in post-menopausal women. The cases reviewed showed that unknown hyper-alpha-fetoprotein was closely related to HNF-1 binding point of AFP in post-menopausal women with cirrhosis (7/11), while the plasma levels of HNF-1α and HNF-1β were not significantly different. CONCLUSION The mutation of the HNF-1 binding point of AFP may lead to an abnormal high expression of AFP by altering the binding of HNF transcription factors, which is closely related to cirrhosis in menopausal women.

中文翻译：

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AFP 基因的 HNF-1 结合点突变会促进绝经后女性的肝硬化。


目的甲胎蛋白（AFP）表达在胚胎期或肝细胞癌变过程中被激活，因此推测AFP是促进细胞增殖或分化的关键内源分子。我们对一个未知的高甲胎蛋白血症家系和部分散发性更年期妇女进行了基因筛查，并探讨了AFP表达与肝硬化的关系。方法 采集家庭成员、肝恶性肿瘤患者和正常对照者的外周血样本。扩增AFP全长序列并直接测序，并与正常对照进行比较。采用ELISA法检测家庭成员、肝癌患者、新生儿、孕妇、正常人血浆中HNF-1α、HNF-1β的含量，评估HNF-1与AFP突变或高表达的关系。结果AFP启动子区c.-200 C>T发生突变，该突变位于AFP肝细胞核因子1（HNF-1）结合位点。所有携带该突变的成员AFP均高于4000 ng/L，但高甲胎蛋白家族排除肝癌。然而，肝硬化发生在绝经后的妇女中。回顾病例显示，绝经后肝硬化女性中未知的高甲胎蛋白与AFP的HNF-1结合点密切相关(7/11)，而血浆中HNF-1α和HNF-1β的水平不显着。不同的。结论 AFP HNF-1结合点突变可能通过改变HNF转录因子的结合导致AFP异常高表达，与绝经期女性肝硬化密切相关。