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. (16th July 2021)

• Record Type: Journal Article
• 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.;
• Is Part Of: Circulation. Volume 14:Number 4(2021)
• Page Start: e003288
• Publication Date: 2021-07-16
• Subjects: carbohydrates -- dyslipidemia -- epidemiology -- genetics -- nutrition -- sugars -- triglyceride; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Genetics -- Periodicals; Cardiovascular Diseases -- genetics; Precision Medicine; Periodical; Fulltext; Internet Resources; Periodicals; Electronic journals; Periodicals; 616.1042
• DOI: 10.1161/CIRCGEN.120.003288
• Languages: English
• ISSNs: 2574-8300

Abstract

Abstract : Supplemental Digital Content is available in the text. 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; P Diff <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; P Diff =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.