Newly identified single-nucleotide polymorphism associated with the transition from nonalcoholic fatty liver disease to liver fibrosis: results from a nested case-control study in the UK biobank
Background Genetic factors may have a significant influence on the likelihood of liver fibrosis in individuals with nonalcoholic fatty liver disease (NAFLD). The present study was conducted to explore how single-nucleotide polymorphism (SNP) impacts the development of fibrosis in those suffering fro...
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Taylor & Francis Group
2025-12-01
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| Series: | Annals of Medicine |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/07853890.2025.2458201 |
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| author | Yitong Ling Yu Xuan Yang Yan Chun Chen Jing Hao Wang Dong Ge Feng Shi Jian Xiang Xiaoyu Zhang Jun Lyu Sha Sha Li |
| author_facet | Yitong Ling Yu Xuan Yang Yan Chun Chen Jing Hao Wang Dong Ge Feng Shi Jian Xiang Xiaoyu Zhang Jun Lyu Sha Sha Li |
| author_sort | Yitong Ling |
| collection | DOAJ |
| description | Background Genetic factors may have a significant influence on the likelihood of liver fibrosis in individuals with nonalcoholic fatty liver disease (NAFLD). The present study was conducted to explore how single-nucleotide polymorphism (SNP) impacts the development of fibrosis in those suffering from NAFLD.Materials and methods Utilizing the UK Biobank dataset, we conducted a nested case-control analysis among NAFLD participants, defining the case group as those with liver fibrosis and cirrhosis during follow-up. For our in vitro investigations, we employed the LX-2 human hepatic stellate cell line. Our procedures included cultivating these cells, employing SAMM50-rs2073080 plasmid techniques to enhance the expression of recently discovered SNPs, and conducting biochemical assays. To quantify gene expression, we used real-time PCR with fluorescence detection.Results The study analyzed data from 5467 participants (1094 cases and 4373 controls). Genome-wide association analysis identified nine significant loci, including the novel rs2073080 variant, strongly associated with NAFLD-associated hepatic fibrosis. In vitro TGF-β modeling revealed significant upregulation of α-SMA and COL1A1, confirming model effectiveness. Oxidative stress markers like elevated malondialdehyde (MDA) and reduced catalase (CAT) and superoxide dismutase (SOD) levels indicated liver damage in the TGF-β group. SAMM50-rs2073080 was upregulated in the NAFLD-associated fibrosis model. In vitro experiments on LX-2 cells showed that SAMM50-rs2073080 overexpression led to increased fibrosis, as indicated by higher cellular MDA levels and lower CAT and SOD levels, compared to the vector group.Conclusion Our research highlights a significant association of SAMM50-rs2073080 with the progression of NAFLD to hepatic fibrosis, and the in vitro experiments further corroborated these findings. |
| format | Article |
| id | doaj-art-8f2e7550cdd0454eb1b404f7852e2697 |
| institution | Kabale University |
| issn | 0785-3890 1365-2060 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Annals of Medicine |
| spelling | doaj-art-8f2e7550cdd0454eb1b404f7852e26972025-02-03T15:45:10ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602025-12-0157110.1080/07853890.2025.2458201Newly identified single-nucleotide polymorphism associated with the transition from nonalcoholic fatty liver disease to liver fibrosis: results from a nested case-control study in the UK biobankYitong Ling0Yu Xuan Yang1Yan Chun Chen2Jing Hao Wang3Dong Ge Feng4Shi Jian Xiang5Xiaoyu Zhang6Jun Lyu7Sha Sha Li8Department of Neurology, Jinan University First Affiliated Hospital, Guangzhou, ChinaDepartment of Pharmacy, Jinan University First Affiliated Hospital, Guangzhou, ChinaDepartment of Pharmacy, Jinan University First Affiliated Hospital, Guangzhou, ChinaDepartment of Pharmacy, Jinan University First Affiliated Hospital, Guangzhou, ChinaDepartment of Pharmacy, Jinan University First Affiliated Hospital, Guangzhou, ChinaDepartment of Pharmacy, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaDepartment of Rheumatology, Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Clinical Research, Jinan University First Affiliated Hospital, Guangzhou, ChinaDepartment of Pharmacy, Jinan University First Affiliated Hospital, Guangzhou, ChinaBackground Genetic factors may have a significant influence on the likelihood of liver fibrosis in individuals with nonalcoholic fatty liver disease (NAFLD). The present study was conducted to explore how single-nucleotide polymorphism (SNP) impacts the development of fibrosis in those suffering from NAFLD.Materials and methods Utilizing the UK Biobank dataset, we conducted a nested case-control analysis among NAFLD participants, defining the case group as those with liver fibrosis and cirrhosis during follow-up. For our in vitro investigations, we employed the LX-2 human hepatic stellate cell line. Our procedures included cultivating these cells, employing SAMM50-rs2073080 plasmid techniques to enhance the expression of recently discovered SNPs, and conducting biochemical assays. To quantify gene expression, we used real-time PCR with fluorescence detection.Results The study analyzed data from 5467 participants (1094 cases and 4373 controls). Genome-wide association analysis identified nine significant loci, including the novel rs2073080 variant, strongly associated with NAFLD-associated hepatic fibrosis. In vitro TGF-β modeling revealed significant upregulation of α-SMA and COL1A1, confirming model effectiveness. Oxidative stress markers like elevated malondialdehyde (MDA) and reduced catalase (CAT) and superoxide dismutase (SOD) levels indicated liver damage in the TGF-β group. SAMM50-rs2073080 was upregulated in the NAFLD-associated fibrosis model. In vitro experiments on LX-2 cells showed that SAMM50-rs2073080 overexpression led to increased fibrosis, as indicated by higher cellular MDA levels and lower CAT and SOD levels, compared to the vector group.Conclusion Our research highlights a significant association of SAMM50-rs2073080 with the progression of NAFLD to hepatic fibrosis, and the in vitro experiments further corroborated these findings.https://www.tandfonline.com/doi/10.1080/07853890.2025.2458201Single-nucleotide polymorphismnonalcoholic fatty liver diseaseliver cirrhosisSAMM50-rs2073080 |
| spellingShingle | Yitong Ling Yu Xuan Yang Yan Chun Chen Jing Hao Wang Dong Ge Feng Shi Jian Xiang Xiaoyu Zhang Jun Lyu Sha Sha Li Newly identified single-nucleotide polymorphism associated with the transition from nonalcoholic fatty liver disease to liver fibrosis: results from a nested case-control study in the UK biobank Annals of Medicine Single-nucleotide polymorphism nonalcoholic fatty liver disease liver cirrhosis SAMM50-rs2073080 |
| title | Newly identified single-nucleotide polymorphism associated with the transition from nonalcoholic fatty liver disease to liver fibrosis: results from a nested case-control study in the UK biobank |
| title_full | Newly identified single-nucleotide polymorphism associated with the transition from nonalcoholic fatty liver disease to liver fibrosis: results from a nested case-control study in the UK biobank |
| title_fullStr | Newly identified single-nucleotide polymorphism associated with the transition from nonalcoholic fatty liver disease to liver fibrosis: results from a nested case-control study in the UK biobank |
| title_full_unstemmed | Newly identified single-nucleotide polymorphism associated with the transition from nonalcoholic fatty liver disease to liver fibrosis: results from a nested case-control study in the UK biobank |
| title_short | Newly identified single-nucleotide polymorphism associated with the transition from nonalcoholic fatty liver disease to liver fibrosis: results from a nested case-control study in the UK biobank |
| title_sort | newly identified single nucleotide polymorphism associated with the transition from nonalcoholic fatty liver disease to liver fibrosis results from a nested case control study in the uk biobank |
| topic | Single-nucleotide polymorphism nonalcoholic fatty liver disease liver cirrhosis SAMM50-rs2073080 |
| url | https://www.tandfonline.com/doi/10.1080/07853890.2025.2458201 |
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