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Background: Liver injury is associated with cholelithiasis, with changes in liver enzyme levels potentially influencing cholelithiasis risk. This study investigates the shared genetic basis between serum levels of four liver enzymes and cholelithiasis using summary data from large-scale genome-wide association studies (GWAS).
Methods: We assessed genetic correlation between liver enzymes and cholelithiasis, and performed local genetic correlation analysis to identify shared genomic regions. A cross-trait meta-analysis identified significant SNPs (single nucleotide polymorphisms) shared between the enzymes and cholelithiasis. To explore causal effects, we applied both two-sample Mendelian randomization and multivariable Mendelian randomization. Heritability-based enrichment analysis was employed to identify tissues and cells jointly associated with liver enzymes and cholelithiasis, while summary-data-based Mendelian Randomization (SMR) was utilized to identify shared genes.
Results: Alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) showed relatively stronger genetic correlations with cholelithiasis compared to the other liver enzymes. Shared SNPs were identified among ALT, GGT, alkaline phosphatase (ALP), and cholelithiasis. Mendelian randomization indicated that a tenfold increase in ALT could raise cholelithiasis risk by 203.4%. The liver was identified as the primary tissue linking these enzymes to cholelithiasis, but no shared cell types were implicated. Several candidate genes, such as SPTLC3, may jointly influence liver enzyme levels and cholelithiasis risk.
Conclusions: Elevated ALT levels may increase cholelithiasis risk. Genetic associations across tissues, genes, and SNPs suggest that liver enzymes could mediate the relationship between liver injury and cholelithiasis risk, providing insights into shared genetic mechanisms with potential implications for future research.
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http://dx.doi.org/10.1186/s12876-025-04162-w | DOI Listing |
Life Sci
September 2025
Department of Experimental Medical Science, Faculty of Medicine, Lund University, 221 84, Lund, Sweden; Wallenberg Center for Molecular Medicine, Faculty of Medicine, Lund University, 221 84, Lund, Sweden. Electronic address:
Aims: Experimental evidence suggests an important role for sphingosine-1-phosphate (S1P) and its generating enzymes sphingosine kinase 1/2 (SphK1/2) in obesity. We and others have shown that plasma S1P levels are elevated in obese mice and humans. Preclinical studies suggest that genetic SphK2 ablation in mice protects from age- and diet-induced obesity and metabolic dysfunction.
View Article and Find Full Text PDFFree Radic Biol Med
September 2025
Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, The First Affiliated Hospital of Guangxi Medical University,Nanning, Guangxi 530021, China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education,
Background: The second most common cause of autosomal recessive early-onset Parkinson's disease (PD) can be attributed to mutations in the PINK1 gene, malfunction of the mitochondria is the key pathological mechanism. Bre1 encodes an E3 ubiquitin ligase, with the discovery of Bre1's role in repairing mitochondrial damage, further investigation into its implications for PD is warranted.
Methods: We used the PINK1B9 drosophila melanogaster as the PD model.
Sci Total Environ
September 2025
Department of Applied Biosciences, Kyungpook National University, Daegu 41566, Republic of Korea; KNU NGS Core Facility, Kyungpook National University, Daegu 41566, Republic of Korea; Microblance Inc., Daegu 41566, Republic of Korea. Electronic address:
Abandoned mines have created extensive idle areas contaminated with heavy metals (HMs). Conventional remediation methods are often costly, environmentally disruptive, and pose risks to human health. As a sustainable alternative, a biological approach utilizing metal-tolerant plant growth-promoting bacteria (mPGPBs) was employed to remediate HM-contaminated soils and assess their biological safety.
View Article and Find Full Text PDFArch Med Res
September 2025
Drug Radiation Research Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
Aim: Radiation-induced hepatotoxicity is a major challenge during radiotherapy. This study aims to evaluate the potential ameliorative outcome and underlying mechanisms of liraglutide (LIRA) in mitigating acute liver injury caused by radiation exposure in vivo.
Methods: Animals were administered LIRA subcutaneously (50 µg/kg/twice daily) for two weeks, and then exposed to whole body γ-radiation (6 Gy) 1 h after the last LIRA dose.
Probiotics Antimicrob Proteins
September 2025
ICAR-Central Institute of Freshwater Aquaculture, Kausalyaganga, Bhubaneswar, Odisha, 751002, India.
This study investigates the effects of probiotics Bacillus subtilis and Bacillus amyloliquefaciens on Labeo rohita fry within a biofloc culture system (BFC). The experimental design consisted of four treatment groups: control (BFC only), T1 (BFC + B. subtilis), T2 (BFC + B.
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