Causal relationship of familial hypercholesterolemia with risk of intestinal vascular disorders: A mendelian randomization study
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) analys...
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Elsevier
2025-03-01
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| Series: | Metabolism Open |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589936825000088 |
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| author | Gang Wei Cheng Zhang Feng-Jie Shen Hua-Qi Guo Lin Liu |
| author_facet | Gang Wei Cheng Zhang Feng-Jie Shen Hua-Qi Guo Lin Liu |
| author_sort | Gang Wei |
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| description | 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)] (P = 0.02) without significant heterogeneity (P = 0.54) and horizontal pleiotropy (P = 0.43). Rs7575840 in 6.5kda upstream of ApoB gene, rs11591147 in PCSK9 gene and rs9644862 in the CDKN2B-AS1 (or named ANRIL; p15AS; PCAT12; CDKN2BAS; CDKN2B-AS; NCRNA00089) 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. |
| format | Article |
| id | doaj-art-e7536ed6ebf040bda927ac8fda19bf0f |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
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| series | Metabolism Open |
| spelling | doaj-art-e7536ed6ebf040bda927ac8fda19bf0f2025-02-06T05:12:40ZengElsevierMetabolism Open2589-93682025-03-0125100352Causal relationship of familial hypercholesterolemia with risk of intestinal vascular disorders: A mendelian randomization studyGang Wei0Cheng Zhang1Feng-Jie Shen2Hua-Qi Guo3Lin Liu4Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China; Corresponding author.Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, ChinaBeijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, ChinaKey Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Hangzhou, 310015, China; Department of Pulmonary and Critical Care Medicine, The Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, ChinaBeijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China; Corresponding author.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)] (P = 0.02) without significant heterogeneity (P = 0.54) and horizontal pleiotropy (P = 0.43). Rs7575840 in 6.5kda upstream of ApoB gene, rs11591147 in PCSK9 gene and rs9644862 in the CDKN2B-AS1 (or named ANRIL; p15AS; PCAT12; CDKN2BAS; CDKN2B-AS; NCRNA00089) 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.http://www.sciencedirect.com/science/article/pii/S2589936825000088Familial hypercholesterolemiaIntestinal vascular diseasesApoBPCSK9CDKN2B-AS1 |
| spellingShingle | Gang Wei Cheng Zhang Feng-Jie Shen Hua-Qi Guo Lin Liu Causal relationship of familial hypercholesterolemia with risk of intestinal vascular disorders: A mendelian randomization study Metabolism Open Familial hypercholesterolemia Intestinal vascular diseases ApoB PCSK9 CDKN2B-AS1 |
| title | Causal relationship of familial hypercholesterolemia with risk of intestinal vascular disorders: A mendelian randomization study |
| title_full | Causal relationship of familial hypercholesterolemia with risk of intestinal vascular disorders: A mendelian randomization study |
| title_fullStr | Causal relationship of familial hypercholesterolemia with risk of intestinal vascular disorders: A mendelian randomization study |
| title_full_unstemmed | Causal relationship of familial hypercholesterolemia with risk of intestinal vascular disorders: A mendelian randomization study |
| title_short | Causal relationship of familial hypercholesterolemia with risk of intestinal vascular disorders: A mendelian randomization study |
| title_sort | causal relationship of familial hypercholesterolemia with risk of intestinal vascular disorders a mendelian randomization study |
| topic | Familial hypercholesterolemia Intestinal vascular diseases ApoB PCSK9 CDKN2B-AS1 |
| url | http://www.sciencedirect.com/science/article/pii/S2589936825000088 |
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