دورية أكاديمية
Phospholipid metabolism-related genotypes of PLA2R1 and CERS4 contribute to nonobese MASLD.
العنوان: | Phospholipid metabolism-related genotypes of PLA2R1 and CERS4 contribute to nonobese MASLD. |
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المؤلفون: | Shao C; Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Ye J; Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Dong Z; Department of Radiology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Liao B; Department of Pathology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Feng S; Department of Radiology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Hu S; Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.; Department of Precision Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China., Zhong B; Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. |
المصدر: | Hepatology communications [Hepatol Commun] 2024 Jun 05; Vol. 8 (6). Date of Electronic Publication: 2024 Jun 05 (Print Publication: 2024). |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Wolters Kluwer Health, Inc Country of Publication: United States NLM ID: 101695860 Publication Model: eCollection Cited Medium: Internet ISSN: 2471-254X (Electronic) Linking ISSN: 2471254X NLM ISO Abbreviation: Hepatol Commun Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2023- : [Philadelphia] : Wolters Kluwer Health, Inc. Original Publication: [Hoboken, NJ] : Wiley Periodicals, Inc. on behalf of the American Association for the Study of Liver Diseases, [2017]- |
مواضيع طبية MeSH: | Genotype* , Receptors, Phospholipase A2*/genetics, Humans ; Male ; Female ; Middle Aged ; Case-Control Studies ; Phospholipids/blood ; Adult ; Obesity/genetics ; Polymorphism, Single Nucleotide ; Fatty Liver/genetics ; Genetic Predisposition to Disease/genetics |
مستخلص: | Background: Abnormal phospholipid metabolism is linked to metabolic dysfunction-associated steatotic liver disease (MASLD) development and progression. We aimed to clarify whether genetic variants of phospholipid metabolism modify these relationships. Methods: This case-control study consecutively recruited 600 patients who underwent MRI-based proton density fat fraction examination (240 participants with serum metabonomics analysis, 128 biopsy-proven cases) as 3 groups: healthy control, nonobese MASLD, and obese MASLD, (n = 200 cases each). Ten variants of phospholipid metabolism-related genes [phospholipase A2 Group VII rs1805018, rs76863441, rs1421378, and rs1051931; phospholipase A2 receptor 1 (PLA2R1) rs35771982, rs3828323, and rs3749117; paraoxonase-1 rs662 and rs854560; and ceramide synthase 4 (CERS4) rs17160348)] were genotyped using SNaPshot. Results: The T-allele of CERS4 rs17160348 was associated with a higher risk of both obese and nonobese MASLD (OR: 1.95, 95% CI: 1.20-3.15; OR: 1.76, 95% CI: 1.08-2.86, respectively). PLA2R1 rs35771982-allele is a risk factor for nonobese MASLD (OR: 1.66, 95% CI: 1.11-1.24), moderate-to-severe steatosis (OR: 3.24, 95% CI: 1.96-6.22), and steatohepatitis (OR: 2.61, 95% CI: 1.15-3.87), while the paraoxonase-1 rs854560 T-allele (OR: 0.50, 95% CI: 0.26-0.97) and PLA2R1 rs3749117 C-allele (OR: 1.70, 95% CI: 1.14-2.52) are closely related to obese MASLD. After adjusting for sphingomyelin level, the effect of the PLA2R1 rs35771982CC allele on MASLD was attenuated. Furthermore, similar effects on the association between the CERS4 rs17160348 C allele and MASLD were observed for phosphatidylcholine, phosphatidic acid, sphingomyelin, and phosphatidylinositol. Conclusions: The mutations in PLA2R1 rs35771982 and CERS4 rs17160348 presented detrimental impact on the risk of occurrence and disease severity in nonobese MASLD through altered phospholipid metabolism. (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.) |
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المشرفين على المادة: | 0 (Receptors, Phospholipase A2) 0 (PLA2R1 protein, human) 0 (Phospholipids) |
تواريخ الأحداث: | Date Created: 20240605 Date Completed: 20240605 Latest Revision: 20240608 |
رمز التحديث: | 20240608 |
مُعرف محوري في PubMed: | PMC11155565 |
DOI: | 10.1097/HC9.0000000000000388 |
PMID: | 38836837 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2471-254X |
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DOI: | 10.1097/HC9.0000000000000388 |