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极低密度脂蛋白胆固醇与总脂质比率和消化性溃疡之间的因果关联:一项双向孟德尔随机化研究。

Causal associations between intermediate very-low-density lipoprotein cholesterol-to-total lipids ratio and peptic ulcer: A bidirectional Mendelian randomization study.

作者信息

Lin Chun-Mei, Meng Qian, Li Ying-Jun, Zhang Shuang-Xi, Luo Qiong-Xi, Dai Zhen-Yu

机构信息

Postgraduate Student, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China.

Department of Gastroenterology, Guangzhou University of Chinese Medicine Shunde Hospital, Foshan 528300, Guangdong Province, China.

出版信息

World J Clin Cases. 2024 Sep 6;12(25):5729-5738. doi: 10.12998/wjcc.v12.i25.5729.

DOI:10.12998/wjcc.v12.i25.5729
PMID:39247748
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11263067/
Abstract

BACKGROUND

Previous epidemiologic investigations have consistently demonstrated a strong association between the ratio of cholesterol to total lipids in medium very-low-density lipoprotein (VLDL) and the occurrence of peptic ulcers (PU). However, the precise causal relationship between these factors remains ambiguous. Consequently, this study aims to elucidate the potential correlation between the ratio of cholesterol to total lipids in medium VLDL and the incidence of peptic ulcer.

AIM

To investigate the ratio of cholesterol to total lipids in medium very-low-density lipoprotein (VLDL) association with PU genetic methods, guiding future clinical research.

METHODS

Genome-wide association study (GWAS) datasets for the ratio of cholesterol to total lipids in intermediate VLDL and peptic ulcer were retrieved from the IEU OpenGWAS project (https://gwas.mrcieu.ac.uk). For the forward Mendelian randomization (MR) analysis, 72 single nucleotide polymorphisms (SNPs) were identified as instrumental variables. These SNPs were selected based on their association with the ratio of cholesterol to total lipids in intermediate VLDL, with peptic ulcer as the outcome variable. Conversely, for the inverse MR analysis, no SNPs were identified with peptic ulcer as the exposure variable and the ratio of cholesterol to total lipids in intermediate VLDL as the outcome. All MR analyses utilized inverse variance weighted (IVW) as the primary analytical method. Additionally, weighted median and MR-Egger methods were employed as supplementary analytical approaches to assess causal effects. Egger regression was used as a supplementary method to evaluate potential directional pleiotropy. Heterogeneity and multiplicity tests were conducted using the leave-one-out method to evaluate result stability and mitigate biases associated with multiple testing.

RESULTS

The genetically predicted ratio of cholesterol to total lipids in medium VLDL was significantly associated with an elevated risk of peptic ulcer (IVW: OR = 2.557, 95%CI = 1.274-5.132, = 0.008). However, no causal association of peptic ulcer with the ratio of cholesterol to total lipids in medium VLDL was observed in the inverse Mendelian randomization analysis.

CONCLUSION

In conclusion, our study reveals a significant association between the ratio of cholesterol to total lipids in medium VLDL and an elevated risk of peptic ulcers. However, further validation through laboratory investigations and larger-scale studies is warranted to strengthen the evidence and confirm the causal relationship between these factors.

摘要

背景

以往的流行病学调查一致表明,中极低密度脂蛋白(VLDL)中胆固醇与总脂质的比例与消化性溃疡(PU)的发生之间存在密切关联。然而,这些因素之间的确切因果关系仍不明确。因此,本研究旨在阐明中VLDL中胆固醇与总脂质的比例与消化性溃疡发病率之间的潜在相关性。

目的

采用遗传方法研究中极低密度脂蛋白(VLDL)中胆固醇与总脂质的比例与PU的关联,为未来的临床研究提供指导。

方法

从IEU OpenGWAS项目(https://gwas.mrcieu.ac.uk)检索中密度VLDL中胆固醇与总脂质比例及消化性溃疡的全基因组关联研究(GWAS)数据集。在正向孟德尔随机化(MR)分析中,72个单核苷酸多态性(SNP)被确定为工具变量。这些SNP是根据它们与中密度VLDL中胆固醇与总脂质比例的关联而选择的,以消化性溃疡作为结果变量。相反,在反向MR分析中,未发现以消化性溃疡为暴露变量、中密度VLDL中胆固醇与总脂质比例为结果的SNP。所有MR分析均采用逆方差加权(IVW)作为主要分析方法。此外,采用加权中位数和MR-Egger方法作为补充分析方法来评估因果效应。Egger回归用作评估潜在定向多效性的补充方法。使用留一法进行异质性和多重性检验,以评估结果稳定性并减轻与多重检验相关的偏差。

结果

遗传预测的中VLDL中胆固醇与总脂质的比例与消化性溃疡风险升高显著相关(IVW:OR = 2.557,95%CI = 1.274 - 5.132,P = 0.008)。然而,在反向孟德尔随机化分析中未观察到消化性溃疡与中VLDL中胆固醇与总脂质比例之间的因果关联。

结论

总之,我们的研究揭示了中VLDL中胆固醇与总脂质的比例与消化性溃疡风险升高之间存在显著关联。然而,有必要通过实验室研究和更大规模的研究进行进一步验证,以加强证据并确认这些因素之间的因果关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e1/11263067/10f01e9b9d9a/WJCC-12-5729-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e1/11263067/10f01e9b9d9a/WJCC-12-5729-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e1/11263067/10f01e9b9d9a/WJCC-12-5729-g001.jpg

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