A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure
Frayling, TM; Beaumont, RN; Jones, SE; et al.Yaghootkar, H; Tuke, MA; Ruth, KS; Casanova, F; West, B; Locke, J; Sharp, S; Ji, Y; Thompson, W; Harrison, J; Etheridge, AS; Gallins, PJ; Jima, D; Wright, F; Zhou, Y; Innocenti, F; Lindgren, CM; Grarup, N; Murray, A; Freathy, RM; Weedon, MN; Tyrrell, J; Wood, AR
Date: 10 April 2018
Journal
Cell Reports
Publisher
Elsevier (Cell Press)
Publisher DOI
Abstract
Fibroblast growth factor 21 (FGF21) is a hormone that has insulin-sensitizing properties. Some trials of FGF21 analogs show weight loss and lipid-lowering effects. Recent studies have shown that a common allele in the FGF21 gene alters the balance of macronutrients consumed, but there was little evidence of an effect on metabolic traits. ...
Fibroblast growth factor 21 (FGF21) is a hormone that has insulin-sensitizing properties. Some trials of FGF21 analogs show weight loss and lipid-lowering effects. Recent studies have shown that a common allele in the FGF21 gene alters the balance of macronutrients consumed, but there was little evidence of an effect on metabolic traits. We studied a common FGF21 allele (A:rs838133) in 451,099 people from the UK Biobank study, aiming to use the human allele to inform potential adverse and beneficial effects of targeting FGF21. We replicated the association between the A allele and higher percentage carbohydrate intake. We then showed that this allele is more strongly associated with higher blood pressure and waist-hip ratio, despite an association with lower total body-fat percentage, than it is with BMI or type 2 diabetes. These human phenotypes of variation in the FGF21 gene will inform research into FGF21’s mechanisms and therapeutic potential.
Institute of Biomedical & Clinical Science
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