| 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 |
| Journal: | Annals of Medicine |
| Published: | 3 Feb 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39898988/ |
| DOI: | https://doi.org/10.1080/07853890.2025.2458201 |
Publication 14445
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Abstract
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.</p>
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.</p>
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.</p>
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.</p>
24 Keywords
- Actins
- Adult
- Aged
- Biological Specimen Banks
- Case-Control Studies
- Catalase
- Cell Line
- Collagen Type I
- Collagen Type I, alpha 1 Chain
- Disease Progression
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Hepatic Stellate Cells
- Humans
- Liver Cirrhosis
- Male
- Middle Aged
- Non-alcoholic Fatty Liver Disease
- Oxidative Stress
- Polymorphism, Single Nucleotide
- Superoxide Dismutase
- UK Biobank
- United Kingdom
9 Authors
- Yitong Ling
- Yu Xuan Yang
- Yan Chun Chen
- Jing Hao Wang
- Dong Ge Feng
- Shi Jian Xiang
- Xiaoyu Zhang
- Jun Lyu
- Sha Sha Li
1 Application
| Application ID | Title |
|---|---|
| 62017 | Risk of cardiovascular disease and all-cause/cause-specific mortality in patients with Non- alcoholic fatty liver disease. |
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