Investigating the shared genetic information between serum concentration levels of liver enzymes and cholelithiasis.

BMC Gastroenterol

Cancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.

Published: August 2025


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12330097PMC
http://dx.doi.org/10.1186/s12876-025-04162-wDOI Listing

Publication Analysis

Top Keywords

liver enzymes
24
enzymes cholelithiasis
24
cholelithiasis risk
16
mendelian randomization
16
cholelithiasis
14
shared genetic
12
liver
11
levels liver
8
enzymes
8
liver injury
8

Similar Publications

Subcutaneous administration of the sphingosine kinase 2 inhibitor ABC294640 has no metabolic benefits in high fat diet-induced obesity in male mice.

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 PDF

Protective Role of Bre1 in Mitochondrial Function and Energy Metabolism in Drosophila Models of Parkinson's disease.

Free 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.

View Article and Find Full Text PDF

Biologically safe restoration of heavy metal-contaminated soils through plant-microbe synergy.

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 PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF