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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

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
Katso/Avaa
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LIPPINCOTT WILLIAMS & WILKINS
doi:10.1161/CIRCGEN.120.003288
URI
https://www.ahajournals.org/doi/10.1161/CIRCGEN.120.003288
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Julkaisun pysyvä osoite on:
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.

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