Title: 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.

Authors: Haslam, Danielle E; Peloso, Gina M; Guirette, Melanie; Imamura, Fumiaki; Bartz, Traci M; Pitsillides, Achilleas N; Wang, Carol A; Li-Gao, Ruifang; Westra, Jason M; Pitkänen, Niina; Young, Kristin L; Graff, Mariaelisa; Wood, Alexis C; Braun, Kim V E; Luan, Jian'an; Kähönen, Mika; Kiefte-de Jong, Jessica C; Ghanbari, Mohsen; Tintle, Nathan; Lemaitre, Rozenn N; Mook-Kanamori, Dennis O; North, Kari; Helminen, Mika; Mossavar-Rahmani, Yasmin; Snetselaar, Linda; Martin, Lisa W; Viikari, Jorma S; Oddy, Wendy H; Pennell, Craig E; Rosendall, Frits R; Ikram, M Arfan; Uitterlinden, Andre G; Psaty, Bruce M; Mozaffarian, Dariush; Rotter, Jerome I; Taylor, Kent D; Lehtimäki, Terho; Raitakari, Olli T; Livingston, Kara A; Voortman, Trudy; Forouhi, Nita G; Wareham, Nick J; de Mutsert, Renée; Rich, Steven S; Manson, JoAnn E; Mora, Samia; Ridker, Paul M; Merino, Jordi; Meigs, James B; Dashti, Hassan S; Chasman, Daniel I; Lichtenstein, Alice H; Smith, Caren E; Dupuis, Josée; Herman, Mark A; McKeown, Nicola M

Published In Circ Genom Precis Med, (2021 08)

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.

PubMed ID: 34270325

MeSH Terms: No MeSH terms associated with this publication