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, D.E.; Peloso, G.M.; Guirette, M.; Imamura, F.; Bartz, T.M.; Pitsillides, A.N.; ... ; McKeown, N.M. (2021)

Article / Letter to editor

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=63599) and the UK Biobank (N=59220) 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 (beta, 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 (beta, 0.06 [95% CI, 0.02-0.09] In-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.

• carbohydrates
• dyslipidemia
• epidemiology
• genetics
• nutrition
• sugars
• triglyceride

• All authors: Haslam, D.E.; Peloso, G.M.; Guirette, M.; Imamura, F.; Bartz, T.M.; Pitsillides, A.N.; Wang, C.A.; Li-Gao, R.F.; Westra, J.M.; Pitkanen, N.; Young, K.L.; Graff, M.; Wood, A.C.; Braun, K.V.E.; Luan, J.A.; Kahonen, M.; Kiefte-de Jong, J.C.; Ghanbari, M.; Tintle, N.; Lemaitre, R.N.; Mook-Kanamori, D.O.; North, K.; Helminen, M.; Mossavar-Rahmani, Y.; Snetselaar, L.; Martin, L.W.; Viikari, J.S.; Oddy, W.H.; Pennell, C.E.; Rosendall, F.R.; Ikram, M.A.; Uitterlinden, A.G.; Psaty, B.M.; Mozaffarian, D.; Rotter, J.I.; Taylor, K.D.; Lehtimaki, T.; Raitakari, O.T.; Livingston, K.A.; Voortman, T.; Forouhi, N.G.; Wareham, N.J.; Mutsert, R. de; Rich, S.S.; Manson, J.E.; Mora, S.; Ridker, P.M.; Merino, J.; Meigs, J.B.; Dashti, H.S.; Chasman, D.I.; Lichtenstein, A.H.; Smith, C.E.; Dupuis, J.; Herman, M.A.; McKeown, N.M.
• Date: 2021-08-01
• Journal: Circulation: Genomic and Precision Medicine
• Volume: 14
• Issue: 4
• Pages: 506 - 516
• DOI: doi:10.1161/CIRCGEN.120.003288
• Link: https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.120.003288