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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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posted on 2023-05-21, 12:06 authored by Haslam, DE, Peloso, GM, Guirette, M, Imamura, F, Bartz, TM, Pitsillides, AN, Wang, CA, Li-Gao, R, Westra, JM, PitkA nen, N, Young, KL, Graff, M, Wood, AC, Braun, KVE, Luan, J, KA hA nen, M, Kiefte-De Jong, JC, Ghanbari, M, Tintle, N, Lemaitre, RN, Mook-Kanamori, DO, North, K, Helminen, M, Mossavar-Rahmani, Y, Snetselaar, L, Martin, LW, Viikari, JS, Wendy OddyWendy Oddy, Pennell, CE, Rosendall, FR, Ikram, MA, Uitterlinden, AG, Psaty, BM, Mozaffarian, D, Rotter, JI, Taylor, KD, LehtimA ki, T, Raitakari, OT, Livingston, KA, Voortman, T, Forouhi, NG, Wareham, NJ, De Mutsert, R, Rich, SS, Manson, JAE, Mora, S, Ridker, PM, Merino, J, Meigs, JB, Dashti, HS, Chasman, DI, Lichtenstein, DI, Smith, CE, Dupuis, J, Herman, MA, McKeown, NM

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:; Unique identifier: NCT00005133, NCT00005121, NCT00005487, and NCT00000479.


Publication title

Circulation: Genomic and Precision Medicine










Menzies Institute for Medical Research


Lippincott Williams & Wilkins

Place of publication


Rights 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.

Repository Status

  • Open

Socio-economic Objectives

Determinants of health; Health inequalities; Health system performance (incl. effectiveness of programs)