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
: 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.
Publisher: LIPPINCOTT WILLIAMS & WILKINS
: 2021
: Circulation: Genomic and Precision Medicine
: CIRCULATION-GENOMIC AND PRECISION MEDICINE
: CIRC-GENOM PRECIS ME
: ARTN e003288
: 14
: 4
: 506
: 516
: 11
: 2574-8300
: 2574-8300
DOI: https://doi.org/10.1161/CIRCGEN.120.003288
: https://www.ahajournals.org/doi/10.1161/CIRCGEN.120.003288
: https://research.utu.fi/converis/portal/detail/Publication/67199418
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.
