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
Creators: name: Mora, S.
name: Merino, J.
name: Dupuis, J.
name: Meigs, J.B.
name: Lehtimäki, T.
name: Helminen, M.
name: Raitakari, O.T.
name: Mossavar-Rahmani, Y.
name: Li-Gao, R.
name: Guirette, M.
name: Pitkänen, N.
name: Lemaitre, R.N.
name: Forouhi, N.G.
name: Mook-Kanamori, D.O.
name: Herman, M.A.
name: Kähönen, M.
name: Oddy, W.H.
name: Mozaffarian, D.
name: Taylor, K.D.
name: Rosendall, F.R.
name: Dashti, H.S.
name: Pitsillides, A.N.
name: Lichtenstein, A.H.
name: Bartz, T.M.
name: North, K.E.
name: Haslam, D.E.
name: Wareham, N.J.
name: De Mutsert, R.
name: Pennell, C.E.
name: Wood, A.C.
name: Luan, J.
name: Chasman, D.I.
name: Uitterlinden, A.G.
name: Rotter, J.I.
name: Peloso, G.M.
name: Imamura, F.
name: Young, K.L.
name: Rich, S.S.
name: Snetselaar, L.
name: Kiefte-De Jong, J.C.
name: Ikram, M.A.
name: Viikari, J.S.
name: Livingston, K.A.
name: Psaty, B.M.
name: Ridker, P.M.
name: Smith, C.E.
name: McKeown, N.M.
name: Voortman, T.
name: Martin, L.W.
name: Wang, C.A.
name: Graff, M.
name: Ghanbari, M.
name: Westra, J.M.
name: Braun, K.V.E.
name: Tintle, N.
name: Manson, J.E.
Publisher: name: Lippincott Williams and Wilkins
Year: 2021

description: 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&lt;0.0001), but not significantly among the lowest SSB consumers (P=0.81; PDiff&lt;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.