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Nutrients
Volume 16
Issue 21
10.3390/nu16213588
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Article

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

by
Yuntong Gao
1,†,
Kun Mao
1,†,
Congying Yang
1,
Xisu Wang
1,
Shixuan Liu
1,
Zimeng Ma
1,
Qi Zhai
1,
Liang Shi
1,
Qian Wu
1,* and
Tianxiao Zhang
1,2,*
1
Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China
2
National Anti-Drug Laboratory, Shaanxi Regional Center, Xi’an 712000, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Nutrients 2024, 16(21), 3588; https://doi.org/10.3390/nu16213588
Submission received: 16 September 2024 / Revised: 8 October 2024 / Accepted: 9 October 2024 / Published: 22 October 2024
(This article belongs to the Special Issue The Impact of Dietary Choline Modulation on Health)
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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: Mendelian randomization; choline metabolites; acute acalculous cholecystitis; low-density lipoprotein; ABCG8 Mendelian randomization; choline metabolites; acute acalculous cholecystitis; low-density lipoprotein; ABCG8

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MDPI and ACS Style

Gao, Y.; Mao, K.; Yang, C.; Wang, X.; Liu, S.; Ma, Z.; Zhai, Q.; Shi, L.; Wu, Q.; Zhang, T. The Causal Relationship Between Choline Metabolites and Acute Acalculous Cholecystitis: Identifying ABCG8 as Colocalized Gene. Nutrients 2024, 16, 3588. https://doi.org/10.3390/nu16213588

AMA Style

Gao Y, Mao K, Yang C, Wang X, Liu S, Ma Z, Zhai Q, Shi L, Wu Q, Zhang T. The Causal Relationship Between Choline Metabolites and Acute Acalculous Cholecystitis: Identifying ABCG8 as Colocalized Gene. Nutrients. 2024; 16(21):3588. https://doi.org/10.3390/nu16213588

Chicago/Turabian Style

Gao, Yuntong, Kun Mao, Congying Yang, Xisu Wang, Shixuan Liu, Zimeng Ma, Qi Zhai, Liang Shi, Qian Wu, and Tianxiao Zhang. 2024. "The Causal Relationship Between Choline Metabolites and Acute Acalculous Cholecystitis: Identifying ABCG8 as Colocalized Gene" Nutrients 16, no. 21: 3588. https://doi.org/10.3390/nu16213588

APA Style

Gao, Y., Mao, K., Yang, C., Wang, X., Liu, S., Ma, Z., Zhai, Q., Shi, L., Wu, Q., & Zhang, T. (2024). The Causal Relationship Between Choline Metabolites and Acute Acalculous Cholecystitis: Identifying ABCG8 as Colocalized Gene. Nutrients, 16(21), 3588. https://doi.org/10.3390/nu16213588

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