A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure

Publication date: 10 April 2018
Source:Cell Reports, Volume 23, Issue 2
Author(s): Timothy M. Frayling, Robin N. Beaumont, Samuel E. Jones, Hanieh Yaghootkar, Marcus A. Tuke, Katherine S. Ruth, Francesco Casanova, Ben West, Jonathan Locke, Seth Sharp, Yingjie Ji, William Thompson, Jamie Harrison, Amy S. Etheridge, Paul J. Gallins, Dereje Jima, Fred Wright, Yihui Zhou, Federico Innocenti, Cecilia M. Lindgren, Niels Grarup, Anna Murray, Rachel M. Freathy, Michael N. Weedon, Jessica Tyrrell, Andrew R. Wood
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.

Graphical abstract

Teaser

Drugs targeting the hormone FGF21 may have beneficial health effects. Variations in human DNA in the FGF21 gene provide an indication of what those effects may be. Here, we show that variation in the FGF21 gene is associated with higher blood pressure and altered body shape, despite lower total body-fat percentage.


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