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

被引：72

作者：

Frayling, Timothy M. ^{[1
]}

Beaumont, Robin N. ^{[1
]}

Jones, Samuel E. ^{[1
]}

Yaghootkar, Hanieh ^{[1
]}

Tuke, Marcus A. ^{[1
]}

Ruth, Katherine S. ^{[1
]}

Casanova, Francesco ^{[1
,2
]}

West, Ben ^{[1
]}

Locke, Jonathan ^{[1
]}

Sharp, Seth ^{[1
]}

Ji, Yingjie ^{[1
]}

Thompson, William ^{[1
]}

Harrison, Jamie ^{[1
]}

Etheridge, Amy S. ^{[3
,4
]}

Gallins, Paul J. ^{[5
]}

Jima, Dereje ^{[5
]}

Wright, Fred ^{[5
]}

Zhou, Yihui ^{[5
]}

Innocenti, Federico ^{[3
,4
]}

Lindgren, Cecilia M. ^{[6
,7
,8
]}

Grarup, Niels ^{[9
]}

Murray, Anna ^{[1
]}

Freathy, Rachel M. ^{[1
]}

Weedon, Michael N. ^{[1
]}

Tyrrell, Jessica ^{[1
,10
]}

Wood, Andrew R. ^{[1
]}

机构：

[1] Univ Exeter, Med Sch, Royal Devon & Exeter Hosp, Genet Complex Traits, RILD Level 3,Barrack Rd, Exeter EX2 5DW, Devon, England

[2] Univ Exeter, Med Sch, Royal Devon & Exeter Hosp, Diabet & Vasc Res Ctr, Barrack Rd, Exeter EX2 5DW, Devon, England

[3] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC USA

[4] Univ N Carolina, Ctr Pharmacogen & Individualized Therapy, Chapel Hill, NC USA

[5] North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA

[6] Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford, England

[7] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[8] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[9] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark

[10] Univ Exeter, Med Sch, Royal Cornwall Hosp, European Ctr Environm & Human Hlth,Knowledge Spa, Truro TR1 3HD, England

来源：

CELL REPORTS | 2018年 / 23卷 / 02期

基金：

英国医学研究理事会; 英国惠康基金; 欧洲研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; GENETIC-VARIANTS; REGULATES METABOLISM; INSULIN-RESISTANCE; RISK; ARCHITECTURE; METAANALYSIS; ADIPOSE; WEIGHT; HYPERTENSION;

D O I：

10.1016/j.celrep.2018.03.070

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：327 / 336

页数：10

共 18 条

[1] Higher Calcium Intake Is Associated with Lower Body Fat Percentage and Cholesterol in Healthy Adolescents
Stallmann-Jorgensen, Inger S.
Johnson, Maribeth H.
Zhu, Haidong
Hall, Patricia
Hatfield-Laube, Jeannie L.
Humphries, Matthew C.
Barbeau, Paule
Gutin, Bernard
Dong, Yanbin
[J]. CIRCULATION, 2009, 119 (10) : E293 - E293
[2] Higher dairy intake is associated with lower body fat during adolescence
Novotny, R
Acharya, S
Grove, JS
Daida, YG
Vogt, TM
[J]. FASEB JOURNAL, 2003, 17 (04): : A746 - A746
[3] Higher Dietary Protein Intake is Associated with Lower Body Fat in the Newfoundland Population
Green, Kristian K.
Shea, Jennifer L.
Vasdev, Sudesh
Randell, Edward
Gulliver, Wayne
Sun, Guang
[J]. CLINICAL MEDICINE INSIGHTS-ENDOCRINOLOGY AND DIABETES, 2010, 3 : 25 - 35
[4] Higher Dietary Essential Amino Acid Intake Is Associated With Lower Body Fat
Wadden, Danny
Cahill, Farrell
Gulliver, Wayne
Sun, Guang
[J]. OBESITY, 2011, 19 : S164 - S164
[5] Identification of alleles associated with higher body fat percentage but lower risk of type 2 diabetes
Yaghootkar, H.
Ji, Y.
Tyrrell, J.
Jones, S. E.
Beaumont, R.
Tuke, M. A.
Ruth, K. S.
Freathy, R. M.
Wood, A. R.
Murray, A.
Weedon, M. N.
Frayling, T. M.
[J]. DIABETOLOGIA, 2017, 60 : S9 - S10
[6] Later energy intake relative to mathematically modeled circadian time is associated with higher percentage body fat
McHill, Andrew W.
Brown, Lindsey S.
Phillips, Andrew J. K.
Barger, Laura K.
Garaulet, Marta
Scheer, Frank A. J. L.
Klerman, Elizabeth B.
[J]. OBESITY, 2023, 31 : 50 - 56
[7] Dietary and Total Calcium Intakes Are Associated with Lower Percentage Total Body and Truncal Fat in Young, Healthy Adults
Skinner, Megan L.
Simpson, Janis A. Randall
Buchholz, Andrea C.
[J]. JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION, 2011, 30 (06) : 484 - 490
[8] Protein Intake Is Associated with Lower Body Fat and Higher Skeletal Muscle Mass in Late Adolescence
Mott, Melanie M.
Singer, Martha R.
Bradlee, M. Loring
Daniels, Stephen R.
Moore, Lynn L.
[J]. FASEB JOURNAL, 2017, 31
[9] Fasting insulin and leptin serum levels are associated with systolic blood pressure independent of percentage body fat and body mass index
Kazumi, T
Kawaguchi, A
Katoh, J
Iwahashi, M
Yoshino, G
[J]. JOURNAL OF HYPERTENSION, 1999, 17 (10) : 1451 - 1455
[10] Soft Drink Consumption in Young Mexican Adults Is Associated with Higher Total Body Fat Percentage in Men but Not in Women
Campos-Ramirez, Cesar
Ramirez-Amaya, Victor
Olalde-Mendoza, Liliana
Palacios-Delgado, Jorge
Anaya-Loyola, Miriam Aracely
[J]. FOODS, 2020, 9 (12)

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