肝细胞核因子 1 alpha 变体是糖尿病和非糖尿病患者罹患肝细胞癌的风险因素

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2024-11-01 DOI:10.1016/j.genrep.2024.102078

Isis Samy Bedira , Ibrahim El Tantawy El Sayed , Olfat M. Hendy , Mohamed Abdel-Samiee , Amany Mohamed Rashad , Ahmed B. Zaid

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引用次数: 0

摘要

背景据报道，HNF1A 基因变异与成熟型糖尿病（DM）的发病有关。许多研究报告称，糖尿病是肝细胞癌（HCC）发病的一个风险因素。目的评估丙型肝炎病毒（HCV）感染者中 HNF1A（肝细胞核因子 1 homeobox A）基因变异与 DM 是否共同导致 HCC 的发生。研究对象和方法这项研究以 140 名受试者为对象，其中 30 人患有无 DM 的 HCC，30 人患有有 DM 的 HCC，40 人患有无 HCV 感染或有 HCC 的 DM；此外，研究还纳入了 80 名年龄和性别匹配的健康志愿者作为对照组。研究人员对所有参与者进行了肝功能检测、肝炎病毒标记物、甲胎蛋白（AFP）、空腹血糖以及实时聚合酶链反应（PCR）检测 HBA1c 和 HNF1A（rs2464196 和 rs1169310）。结果患者组（DM、HCC、HCC + DM）中 HNF1A rs2464196（AA）基因型的频率明显高于对照组（分别为 P = 0.006、P = 0.018、P < 0.001）。在患者组（DM、HCC、HCC + DM）中，rs 2464196 的联合显性模式（AA + GA）明显高于（GG）基因型，高于对照组。此外，与 DM 或 HCC 患者组相比，AA 基因型在 HCC + DM 中更为普遍（73%）。与此相反，HNF1A rs1169310（TT、TC 或 CC 基因型）在四个研究组及其 T 或 C 等位基因分布之间没有显著差异。相反，在本研究中，HNF1A rs1169310 多态性并不是一个重要的风险因素。不过，由于我们的研究仅限于埃及参与者，因此需要对其他种族群体进行更多研究。此外，建议对 HNF1A 的其他变异进行大规模研究，以明确该基因在 HCC 发病中的作用。

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Hepatocyte nuclear factor 1 alpha variants as risk factor for hepatocellular carcinoma development with and without diabetes mellitus

Background

HNF1A gene variants have been reported to be involved in developing mature onset diabetes mellitus (DM). Many studies reported the role of DM as a risk factor for hepatocellular carcinoma (HCC) development. To date, it has not been reported whether HNF1A gene variants are associated with the risk of DM in cirrhotic patients and their subsequent HCC.

Objective

To evaluate the HNF1A (the hepatocyte nuclear factor 1 homeobox A) genetic variants as a cofactor with DM for HCC development in hepatitis C virus (HCV)-infected patients.

Subjects and methods

This study was conducted on 140 subjects; 30 had HCC without DM, 30 HCC with DM, and 40 patients had DM with no HCV infection or had HCC; in addition, 80 healthy volunteers with matched ages and genders were enrolled in the study as a control group. Liver function tests, hepatitis viral markers, alpha-fetoprotein (AFP), fasting sugar and HBA1c and HNF1A (rs2464196 and rs1169310) using real-time polymerase chain reaction (PCR) were done for all participants.

Results

The frequency of HNF1A rs2464196 (AA) genotype in patient groups (DM, HCC, HCC + DM) was significantly higher compared to the control group (P = 0.006, P = 0.018, P < 0.001 respectively). The combined dominant model (AA + GA) of rs 2464196 was significantly higher than the (GG) genotype in patient groups (DM, HCC, HCC + DM) than the control group. In addition, the frequency of the AA genotype is more prevalent in HCC + DM (73 %) compared to the group of DM or HCC patients. In contrast, the HNF1A rs1169310 (TT, TC or CC genotypes) showed no significant difference among the four studied groups and their T or C allele distributions.

Conclusion

This finding suggested that the HNF1A rs2464196 (AA) genotype could be associated with DM and may raise the possibility of HCC development among HCV-infected patients who harbour this genotype more than (GG). On the contrary, the HNF1A rs1169310 polymorphism was of no significance as a risk factor in the current study. However, as we limited our study to Egyptian participants, more research on other ethnic groups would be required. Also, large scale studies are recommended on other variants of HNF1A to clarify the role of this gene in HCC development.

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.