Causal Relationship of Familial Hypercholesterolemia with Risk of Intestinal Vascular Disorders: A Mendelian Randomization Study

Overview

Journal Metabol Open

Specialty Endocrinology

Date 2025 Feb 24

PMID 39991491

Authors

Gang Wei

Cheng Zhang

Feng-Jie Shen

Hua-Qi Guo

Lin Liu

Affiliations

Soon will be listed here.

Abstract

Background: The causal relationship between the familial hypercholesterolemia (FH) and intestinal vascular diseases was unnoticed. This study aims to investigate the cause-and-effect relationship of FH with risk of intestinal vascular diseases in human.

Methods: A Mendelian randomization (MR) analysis was performed by extracting summary-level datasets for FH or FH concurrently with ischemic heart disease (IHD) and intestinal vascular diseases from the FinnGen study including 329,115, 316,290 and 350,505 individuals. The inverse-variance weighted (IVW) method and the weighted median method were applied to analyze the causal relationships between FH or FH concurrently with IHD and the risk of intestinal vascular diseases. Cochran's Q statistic method and MR-Egger regression were used to assess heterogeneity and pleiotropy.

Results: The IVW method demonstrated that FH was significantly associated with higher odds of intestinal vascular diseases [OR (95%CI): 1.22 (1.03, 1.45)] ( = 0.02) without significant heterogeneity ( = 0.54) and horizontal pleiotropy ( = 0.43). Rs7575840 in 6.5kda upstream of gene, rs11591147 in gene and rs9644862 in the (or named ; ; ; ; ) gene were illustrated to mostly influence the risk of intestinal vascular diseases. However, no significant causal relationship between FH concurrently with IHD and intestinal vascular diseases was observed.

Conclusion: In conclusion, FH was causally positive-associated with the increased risk of intestinal vascular diseases, revealing a potential unfortunate outcome for FH. Therefore, patients with FH should pay closely attention to the risk of intestinal vascular diseases. Our study may provide evidence for new diagnostic and therapeutic strategies in clinical practices.

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