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: July 2021

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.