04415nas a2200805 4500008004100000022001400041245024200055210006900297260001300366300001200379490000700391520195900398100002402357700002002381700002202401700002102423700002002444700003002464700001902494700002002513700002102533700002102554700002202575700002202597700002002619700002002639700001802659700002002677700003202697700002102729700001902750700002402769700002902793700001602822700001902838700002902857700002202886700002002908700002202928700001902950700002202969700002402991700002003015700002803035700002003063700002503083700002203108700002003130700002203150700002303172700002403195700002003219700002103239700002103260700002303281700002003304700002103324700001603345700002003361700001803381700002003399700002203419700002303441700002703464700002003491700001903511700002003530700002303550856003603573 2021 eng d a2574-830000aSugar-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.0 aSugarSweetened Beverage Consumption May Modify Associations Betw c2021 Aug ae0032880 v143 a
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 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 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 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; <0.0001), but not significantly among the lowest SSB consumers (=0.81; <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, =0.001) but not the lowest SSB consumers (=0.84; =0.0005).
CONCLUSIONS: Our results identified genetic variants in the 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.
1 aHaslam, Danielle, E1 aPeloso, Gina, M1 aGuirette, Melanie1 aImamura, Fumiaki1 aBartz, Traci, M1 aPitsillides, Achilleas, N1 aWang, Carol, A1 aLi-Gao, Ruifang1 aWestra, Jason, M1 aPitkänen, Niina1 aYoung, Kristin, L1 aGraff, Mariaelisa1 aWood, Alexis, C1 aBraun, Kim, V E1 aLuan, Jian'an1 aKähönen, Mika1 ade Jong, Jessica, C Kiefte-1 aGhanbari, Mohsen1 aTintle, Nathan1 aLemaitre, Rozenn, N1 aMook-Kanamori, Dennis, O1 aNorth, Kari1 aHelminen, Mika1 aMossavar-Rahmani, Yasmin1 aSnetselaar, Linda1 aMartin, Lisa, W1 aViikari, Jorma, S1 aOddy, Wendy, H1 aPennell, Craig, E1 aRosendall, Frits, R1 aIkram, Arfan, M1 aUitterlinden, André, G1 aPsaty, Bruce, M1 aMozaffarian, Dariush1 aRotter, Jerome, I1 aTaylor, Kent, D1 aLehtimäki, Terho1 aRaitakari, Olli, T1 aLivingston, Kara, A1 aVoortman, Trudy1 aForouhi, Nita, G1 aWareham, Nick, J1 ade Mutsert, Renée1 aRich, Steven, S1 aManson, JoAnn, E1 aMora, Samia1 aRidker, Paul, M1 aMerino, Jordi1 aMeigs, James, B1 aDashti, Hassan, S1 aChasman, Daniel, I1 aLichtenstein, Alice, H1 aSmith, Caren, E1 aDupuis, Josée1 aHerman, Mark, A1 aMcKeown, Nicola, M uhttps://chs-nhlbi.org/node/8830