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Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants in the CHREBP (Carbohydrate Responsive Element Binding Protein) Locus and HDL-C (High-Density Lipoprotein Cholesterol) and Triglyceride Concentrations

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Haslam, DE and Peloso, GM and Guirette, M and Imamura, F and Bartz, TM and Pitsillides, AN and Wang, CA and Li-Gao, R and Westra, JM and PitkA nen, N and Young, KL and Graff, M and Wood, AC and Braun, KVE and Luan, J and KA hA nen, M and Kiefte-De Jong, JC and Ghanbari, M and Tintle, N and Lemaitre, RN and Mook-Kanamori, DO and North, K and Helminen, M and Mossavar-Rahmani, Y and Snetselaar, L and Martin, LW and Viikari, JS and Oddy, WH and Pennell, CE and Rosendall, FR and Ikram, MA and Uitterlinden, AG and Psaty, BM and Mozaffarian, D and Rotter, JI and Taylor, KD and LehtimA ki, T and Raitakari, OT and Livingston, KA and Voortman, T and Forouhi, NG and Wareham, NJ and De Mutsert, R and Rich, SS and Manson, JAE and Mora, S and Ridker, PM and Merino, J and Meigs, JB and Dashti, HS and Chasman, DI and Lichtenstein, DI and Smith, CE and Dupuis, J and Herman, MA and McKeown, NM, Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants in the CHREBP (Carbohydrate Responsive Element Binding Protein) Locus and HDL-C (High-Density Lipoprotein Cholesterol) and Triglyceride Concentrations, Circulation: Genomic and Precision Medicine, 14, (4) pp. 506-516. ISSN 2574-8300 (2021) [Refereed Article]


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Copyright Statement

2021 The Authors. Circulation: Genomic and Precision Medicine is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs license.

DOI: doi:10.1161/CIRCGEN.120.003288

Abstract

Background:ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia.

Methods:Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake.

Results: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (β, 2.12 [95% CI, 1.16-3.07] mg/dL per allele; P<0.0001), but not significantly among the lowest SSB consumers (P=0.81; PDiff <0.0001). Similar results were observed for 2 additional variants (rs35709627 and rs71556736). For triglyceride, rs55673514 was positively associated with triglyceride concentrations only among the highest SSB consumers (β, 0.06 [95% CI, 0.02-0.09] ln-mg/dL per allele, P=0.001) but not the lowest SSB consumers (P=0.84; PDiff=0.0005).

Conclusions: Our results identified genetic variants in the CHREBP locus that may protect against SSB-associated reductions in HDL-C and other variants that may exacerbate SSB-associated increases in triglyceride concentrations. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005133, NCT00005121, NCT00005487, and NCT00000479.

Item Details

Item Type:Refereed Article
Keywords:carbohydrates, dyslipidemia, epidemiology, genetics, nutrition, sugars, triglyceride
Research Division:Biomedical and Clinical Sciences
Research Group:Nutrition and dietetics
Research Field:Food properties (incl. characteristics and health benefits)
Objective Division:Health
Objective Group:Evaluation of health and support services
Objective Field:Determinants of health
UTAS Author:Oddy, WH (Professor Wendy Oddy)
ID Code:152442
Year Published:2021
Web of Science® Times Cited:4
Deposited By:Medicine
Deposited On:2022-08-19
Last Modified:2022-11-29
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