1. Functional Impact of the FADS1 rs174546 Single Nucleotide Polymorphism on Serum Lipid Levels: Insights from Molecular Mechanisms and Therapeutic Perspectives in Korean Population.
- Author
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Lee KH, Kim SH, Park S, Jang HJ, Kim MJ, Yang HJ, Hur HJ, Kim JH, and Kim MS
- Subjects
- Humans, Republic of Korea, Male, Female, Middle Aged, MicroRNAs genetics, Hypertriglyceridemia genetics, Hypertriglyceridemia blood, Asian People genetics, Adult, Fatty Acid Desaturases genetics, Delta-5 Fatty Acid Desaturase, Polymorphism, Single Nucleotide, Triglycerides blood
- Abstract
Scope: Single nucleotide polymorphisms (SNP) in the fatty acid desaturase 1 (FADS1) gene is suggested as risk factor of metabolic diseases in genome-wide association studies (GWAS). This study hypothesized that FADS1_rs174546T associates with serum triglycerides (TG) in Korean Genome and Epidemiology Study (KoGES). In addition, functional study of SNP genotypes in cultured cells is performed., Methods and Results: FADS1_rs174546T is associated with high level of serum TG (effect size of variant: 6.48 ± 1.84 mg dL
-1 ) in Korean individuals (normotriglyceridemia, n = 5128; hypertriglyceridemia, n = 3714). Functional study in cells with FADS1_rs174546T, shows reduced transcriptional activity, when compared with rs174546C. MiR-6728-3p, which is predicted to bind with rs174546T, decreases transcriptional activity of rs174546T but not in rs174546C, and it is reversed by miR-6728-3p inhibitor. Formononetin is selected as binding molecule to 3'-UTR of FADS1 and increases luciferase activity in both rs174546 (C/T). Moreover, formononetin compensates for the reduced luciferase activity by rs174546T and miR-6728-3p. Formononetin also increases endogenous FADS1 expression and long-chain polyunsaturated fatty acid (LC-PUFA) ratio., Conclusion: FADS1_rs174546T is a crucial risk factor for hypertriglyceridemia in the Koreans potentially through the interaction with miR-6728-3p. Formononetin can be a potent dietary intervention to prevent and improve hypertriglyceridemia in both rs174546 (C/T) populations., (© 2024 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)- Published
- 2024
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