The Causal Relationship Between Choline Metabolites and Acute Acalculous Cholecystitis: Identifying ABCG8 as Colocalized Gene – PubMed Black Hawk Supplements

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CONCLUSIONS: There is a causal relationship between choline metabolites and cholecystitis, mediated through the protective action of LDL. Our results suggest that ABCG8 may play a role in the development of non-calculous cholecystitis.
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The Causal Relationship Between Choline Metabolites and Acute Acalculous Cholecystitis: Identifying ABCG8 as Colocalized Gene - PubMed

The Causal Relationship Between Choline Metabolites and Acute Acalculous Cholecystitis: Identifying ABCG8 as Colocalized Gene

Yuntong Gao et al. Nutrients. .

Abstract

Background: Acute acalculous cholecystitis (AAC) is a type of cholecystitis with high mortality rate while its pathogenesis remains complex. Choline is one of the essential nutrients and is related to several diseases. This study aimed to explore the causal relationship between choline metabolites and AAC and its potential mechanisms.

Methods: This research utilized the two-sample Mendelian randomization method to investigate the causal relationship between choline metabolites and AAC. Additionally, multivariable Mendelian randomization and mediated Mendelian randomization were used to explore potential confounding effects from low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TGs), and coronary artery disease (CAD). Linkage disequilibrium score regression (LDSC), co-localization analysis, and enrichment analysis were used to investigate relevant molecular mechanisms.

Results: There is a negative causal relationship between total choline (OR [95%CI] = 0.9982 [0.9974, 0.9990], p = 0.0023), phosphatidylcholine (OR [95%CI] = 0.9983 [0.9976-0.9991], p = 0.0040), sphingomyelin (OR [95%CI] = 0.9980 [0.9971-0.9988], p = 0.0001), and AAC. The mediating effects of LDL were -0.0006 for total choline, -0.0006 for phosphatidylcholine, and -0.0008 for sphingomyelin, indicating a protective effect of total choline, phosphatidylcholine, and sphingomyelin on AAC. Colocalized SNP rs75331444, which is mapped to gene ABCG8, was identified for total choline (PPH4 = 0.8778) and sphingomyelin (PPH4 = 0.9344).

Conclusions: There is a causal relationship between choline metabolites and cholecystitis, mediated through the protective action of LDL. Our results suggest that ABCG8 may play a role in the development of non-calculous cholecystitis.

Keywords: ABCG8; Mendelian randomization; acute acalculous cholecystitis; choline metabolites; low-density lipoprotein.

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Conflict of interest statement

All authors declare no conflicts of interests. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1

Conceptual framework of this study.

Figure 2
Figure 2

Analysis of the relationship between choline metabolites and cholecystitis by Mendelian randomization analysis (results corresponding to five different methods).

Figure 3
Figure 3

Manhattan plots for colocalization analysis. (A) Manhattan plot of selected SNP associations with PPH4 at the genome-wide scale with yellow and purple dots to distinguish between adjacent chromosomal locations. (B) Locus comparison plot for the COLOC analysis of the notable colocalization regions (PPH4 > 0.9).

Figure 4
Figure 4

Bubble plots for enrichment analysis of genes and their related genes obtained from colocalization analysis. (A) GO enrichment analysis, including biological processes (BPs), cellular components (CCs), and molecular functions (MFs). (B) KEGG enrichment analysis.

References

    1. Jia F., Ma Y., Liu Y. Association of milk consumption with the incidence of cholelithiasis disease in the US adult population. BMC Public Health. 2023;23:1639. doi: 10.1186/s12889-023-16615-6. – DOI – PMC – PubMed
    1. O’Connor O.J., Maher M.M. Imaging of Cholecystitis. Am. J. Roentgenol. 2011;196:W367–W374. doi: 10.2214/AJR.10.4340. – DOI – PubMed
    1. Elwood D.R. Cholecystitis. Surg. Clin. N. Am. 2008;88:1241–1252. doi: 10.1016/j.suc.2008.07.008. – DOI – PubMed
    1. Frazee R.C., Nagorney D.M., Mucha P. Acute acalculous cholecystitis. Mayo Clin. Proc. 1989;64:163–167. doi: 10.1016/S0025-6196(12)65670-5. – DOI – PubMed
    1. Barie P.S., Eachempati S.R. Acute acalculous cholecystitis. Curr. Gastroenterol. Rep. 2003;5:302–309. doi: 10.1007/s11894-003-0067-x. – DOI – PubMed

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Grants and funding

This study was supported by the Hygiene and Health Care Scientific Research Program of Shaanxi Province (2022D010) and Scientific Research Program of Shaanxi provincial center for disease control and prevention (HXDSH20232686). The funding body did not participate in the design, conduct, or writing of the study.

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The Causal Relationship Between Choline Metabolites and Acute Acalculous Cholecystitis: Identifying ABCG8 as Colocalized Gene – PubMed