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

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. 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.

SUBMITTER: Frayling TM

PROVIDER: S-EPMC5912948 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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

Frayling Timothy M TM Beaumont Robin N RN Jones Samuel E SE Yaghootkar Hanieh H Tuke Marcus A MA Ruth Katherine S KS Casanova Francesco F West Ben B Locke Jonathan J Sharp Seth S Ji Yingjie Y Thompson William W Harrison Jamie J Etheridge Amy S AS Gallins Paul J PJ Jima Dereje D Wright Fred F Zhou Yihui Y Innocenti Federico F Lindgren Cecilia M CM Grarup Niels N Murray Anna A Freathy Rachel M RM Weedon Michael N MN Tyrrell Jessica J Wood Andrew R AR

Cell reports 20180401 2

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 benefi ...[more]

PMID: 29641994

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Project description:BackgroundObesity and diabetes mellitus (DM) are public health concerns in Mexico of top-level priority due to their high prevalence and their growth rate in recent decades. The accumulation of adipose tissue leads to an unbalanced release of pro-oxidant factors, which causes cellular damage and favors the development of comorbidities. Recent evidence suggests that oxidative stress also promotes the accumulation of adipose tissue and the development of insulin resistance. The objective of this study is to evaluate the association between usual intake of antioxidant nutrients, specifically vitamins A, C, E and magnesium with body mass index (BMI), waist circumference (WC) and serum glucose concentrations in a representative sample of Mexican adults.MethodologyWe analyzed data on diet, BMI, WC and serum glucose from the Mexican National Health and Nutrition Survey 2012. Analysis included 20- to 65-year-old adults without a known diagnosis of DM (n = 1573). Dietary information was obtained using the five-step multiple-pass method developed by the United States Department of Agriculture and adapted to the Mexican context. Nutrient usual intake distributions were estimated using the Iowa State University method, through the "Software for Intake Distribution Estimation" (PC-Side) v.1.02. Associations were analyzed using multivariate regression models.ResultsHigher dietary magnesium intake was associated with lower markers of adiposity, so that an increase in 10 mg per 1000 kcal/day of magnesium was associated with an average decrease in BMI of 0.72% (95% CI: -1.36, - 0.08) and 0.49 cm (95% CI: -0.92, - 0.07) of WC. Additionally, in women with normal glucose concentrations, an increase in magnesium intake was associated with an average decrease in serum glucose by 0.59% (95% CI: -1.08, - 0.09).ConclusionThe results suggest that magnesium intake is associated with lower BMI, WC and serum glucose in Mexican population. However, more studies are required to elucidate the nature of this association.

Project description:There is conflicting evidence about the association between dairy products and cardiometabolic risk (CMR). We aimed to assess the association of total dairy intake with CMR factors and to investigate the association of unfermented and fermented dairy intake with CMR in Asian Indians who are known to have greater susceptibility to type 2 diabetes and cardiovascular diseases compared to white Europeans. The study comprised 1033 Asian Indian adults with normal glucose tolerance chosen from the Chennai Urban Rural Epidemiological Study (CURES). Dietary intake was assessed using a validated open-ended semi-quantitative food frequency questionnaire. Metabolic syndrome (MS) was diagnosed based on the new harmonising criteria using central obesity, dyslipidaemia [low high-density lipoprotein cholesterol (HDL) and increased serum triglycerides (TG)], hypertension and glucose intolerance. Increased consumption of dairy (≥5 cups per day of total, ≥4 cups per day of unfermented or ≥2 cups per day of fermented dairy) was associated with a lower risk of high fasting plasma glucose (FPG) [hazards ratio (HR), 95% confidence interval (CI): 0.68, 0.48-0.96 for total dairy; 0.57, 0.34-0.94 for unfermented dairy; and 0.64, 0.46-0.90 for fermented dairy; p < 0.05 for all] compared to a low dairy intake (≤1.4 cups per day of total dairy; ≤1 cup per day of unfermented dairy; and ≤0.1 cup per day of fermented dairy). A total dairy intake of ≥5 cups per day was also protective against high blood pressure (BP) (HR: 0.65, 95% CI: 0.43-0.99, p < 0.05), low HDL (HR: 0.63, 95% CI: 0.43-0.92, p < 0.05) and MS (HR: 0.71, 95% CI: 0.51-0.98, p < 0.05) compared to an intake of ≤1.4 cups per day. A high unfermented dairy intake (≥4 cups per day) was also associated with a lower risk of high body mass index (BMI) (HR: 0.52, 95% CI: 0.31-0.88, p < 0.05) compared to a low intake (≤1 cup per day), while a reduced risk of MS was observed with a fermented dairy intake of ≥2 cups per day (HR: 0.71, 95% CI: 0.51-0.98, p < 0.05) compared to an intake of ≤0.1 cup per day. In summary, increased consumption of dairy was associated with a lower risk of MS and components of CMR.

Dataset Information

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

Publications

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

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