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
Bartz Traci M.; Braun Kim V.E.; Chasman Daniel I.; Dashti Hassan S.; Dupuis Josée; Forouhi Nita G.; Ghanbari Mohsen; Graff Mariaelisa; Guirette Melanie; Haslam Danielle E.; Helminen Mika; Herman Mark A.; Ikram M. Arfan; Imamura Fumiaki; Kiefte-de Jong Jessica C.; Kähönen Mika; Lehtimäki Terho; Lemaitre Rozenn N.; Li-Gao Ruifang; Lichtenstein Alice H.; Livingston Kara A.; Luan Jian’an; Manson JoAnn E.; Martin Lisa W.; McKeown Nicola M.; Meigs James B.; Merino Jordi; Mook-Kanamori Dennis O.; Mora Samia; Mossavar-Rahmani Yasmin; Mozaffarian Dariush; North Kari; Oddy Wendy H.; Peloso Gina M.; Pennell Craig E.; Pitkänen Niina; Pitsillides Achilleas N.; Psaty Bruce M.; Raitakari Olli T.; Rich Steven S.; Ridker Paul M.; Rosendall Frits R.; Rotter Jerome I.; Smith Caren E.; Snetselaar Linda; Taylor Kent D.; Tintle Nathan; Uitterlinden Andre G; Viikari Jorma S.; Voortman Trudy; Wang Carol A.; Wareham Nick J.; Westra Jason M.; Wood Alexis C.; Young Kristin L.; de Mutsert Renée
https://urn.fi/URN:NBN:fi-fe2021093048873
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19204]