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,Circulation: Genomic and Precision Medicine

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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
Circulation: Genomic and Precision Medicine ( IF 6.0 ) Pub Date : 2021-07-16 , DOI: 10.1161/circgen.120.003288
Danielle E Haslam _{1,

2,

3} , Gina M Peloso ₄ , Melanie Guirette ₁ , Fumiaki Imamura ₅ , Traci M Bartz _{6,

7} , Achilleas N Pitsillides ₄ , Carol A Wang ₈ , Ruifang Li-Gao ₉ , Jason M Westra ₁₀ , Niina Pitkänen _{11,

12} , Kristin L Young ₁₃ , Mariaelisa Graff ₁₃ , Alexis C Wood ₁₄ , Kim V E Braun ₁₅ , Jian'an Luan ₅ , Mika Kähönen _{16,

17} , Jessica C Kiefte-de Jong _{15,

18} , Mohsen Ghanbari ₁₅ , Nathan Tintle ₁₀ , Rozenn N Lemaitre ₇ , Dennis O Mook-Kanamori _{9,

18} , Kari North _{13,

19} , Mika Helminen _{20,

21} , Yasmin Mossavar-Rahmani ₂₂ , Linda Snetselaar ₂₃ , Lisa W Martin ₂₄ , Jorma S Viikari _{25,

26} , Wendy H Oddy ₂₇ , Craig E Pennell _{8,

28} , Frits R Rosendall ₉ , M Arfan Ikram ₁₅ , Andre G Uitterlinden ₂₉ , Bruce M Psaty _{7,

30,

31} , Dariush Mozaffarian ₃₂ , Jerome I Rotter ₃₃ , Kent D Taylor ₃₃ , Terho Lehtimäki _{34,

35} , Olli T Raitakari _{12,

36,

37} , Kara A Livingston ₁ , Trudy Voortman , Nita G Forouhi ₅ , Nick J Wareham ₅ , Renée de Mutsert ₉ , Steven S Rich ₃₈ , JoAnn E Manson _{2,

39,

40} , Samia Mora _{39,

41} , Paul M Ridker _{39,

41} , Jordi Merino _{42,

43,

44,

45,

46} , James B Meigs _{42,

43,

44,

47} , Hassan S Dashti _{42,

46,

48} , Daniel I Chasman ₃₉ , Alice H Lichtenstein ₄₉ , Caren E Smith , Josée Dupuis ₄ , Mark A Herman ₅₀ , Nicola M McKeown ₁

Affiliation

Nutritional Epidemiology Program (D.E.H., M. Guirette, K.A.L., N.M.M.), Tufts University, Boston, MA.
Channing Division of Network Medicine (D.E.H., J.E.M.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Department of Nutrition (D.E.H.), Harvard T.H. Chan School of Public Health, Boston, MA.
Department of Biostatistics, Boston University School of Public Health, MA (G.M.P., A.N.P., J.D.).
Medical Research Council Epidemiology Unit, University of Cambridge, United Kingdom (F.I., J.L., N.G.F., N.J.W.).
Cardiovascular Health Research Unit, Departments of Biostatistics (T.M.B.), University of Washington, Seattle.
Department of Medicine (T.M.B., R.N.L., B.M.P.), University of Washington, Seattle.
School of Medicine and Public Health, Faculty of Medicine and Health, The University of Newcastle, NSW, Australia (C.A.W., C.E.P.).
Department of Clinical Epidemiology (R.L.G., D.O.M.-K., F.R.R., R.dM.), Leiden University Medical Center, the Netherlands.
Dordt University, Sioux Center, IA (J.M.W., N.T.).
Auria Biobank (N.P.), University of Turku, Finland.
Research Centre of Applied and Preventive Cardiovascular Medicine (N.P., O.T.R.), University of Turku, Finland.
Department of Epidemiology, Gillings School of Global Public Health (K.L.Y., M. Graff, K.N.), University of North Carolina, Chapel Hill.
USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (A.C.W.).
Department of Epidemiology (K.V.E.B., J.C.K.-d.J., M. Ghanbari, M.A.I.), Erasmus MC University Medical Center Rotterdam, the Netherlands.
Department of Clinical Physiology (M.K.), Tampere University Hospital, Finland.
Department of Clinical Physiology (M.K.), Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Finland.
Department of Public Health and Primary Care (J.C.L.d.J., D.O.M.-K.), Leiden University Medical Center, the Netherlands.
Carolina Center for Genome Science (K.N.), University of North Carolina, Chapel Hill.
Research Development and Innovation Centre (M.H.), Tampere University Hospital, Finland.
Faculty of Social Sciences, Health Sciences, Tampere University, Finland (M.H.).
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (Y.M.-R.).
Department of Epidemiology, University of Iowa, Iowa City (L.S.).
George Washington University School of Medicine and Health Sciences, Washington, D.C. (L.W.M.).
Department of Medicine (J.S.V.), University of Turku, Finland.
Division of Medicine (J.S.V.), Turku University Hospital, Finland.
Menzies Institute for Medical Research, University of Tasmania, HOB, Australia (W.H.O.).
Nutrition and Genomics Laboratory (C.E.S.), Tufts University, Boston, MA.
Department of Internal Medicine (A.G.U.), Erasmus MC University Medical Center Rotterdam, the Netherlands.
Departments of Epidemiology and Health Services (B.M.P.), University of Washington, Seattle.
Kaiser Permanente Washington Health Research Institute, Seattle, WA (B.M.P.).
Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, and Friedman School of Nutrition Science and Policy (D.M.), Tufts University, Boston, MA.
The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA (J.I.R., K.D.T.).
Department of Clinical Chemistry (T.L.), Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Finland.
Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland (T.L.).
Centre for Population Health Research (O.T.R.), University of Turku, Finland.
Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Finland.
Center for Public Health Genomics and Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville (S.S.R.).
Division of Preventive Medicine (J.E.M., S.M., P.M.R., D.I.C.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Department of Epidemiology (J.E.M.), Harvard T.H. Chan School of Public Health, Boston, MA.
Cardiovascular Division of Medicine and Center for Lipid Metabolomics (S.M., P.M.R.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Program in Medical and Population Genetics (J.M., J.B.M., H.S.D.), Broad Institute of MIT and Harvard, Cambridge, MA.
Program in Metabolism (J.M., J.B.M.), Broad Institute of MIT and Harvard, Cambridge, MA.
Department of Medicine, Harvard Medical School, Boston, MA (J.M., J.B.M.).
Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.M.).
Diabetes Unit and Center for Genomic Medicine (J.M., H.S.D.), Massachusetts General Hospital and Harvard Medical School, Boston.
Division of General Internal Medicine (J.B.M.), Massachusetts General Hospital and Harvard Medical School, Boston.
Department of Anesthesia, Critical Care and Pain Medicine (H.S.D.), Massachusetts General Hospital and Harvard Medical School, Boston.
Cardiovascular Nutrition Laboratory (A.H.L.), Tufts University, Boston, MA.
Division Of Endocrinology, Metabolism, and Nutrition, Department of Medicine and Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC (M.A.H.).

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.

中文翻译：

含糖饮料的消费可能会改变 CHREBP（碳水化合物反应元件结合蛋白）基因座中的遗传变异与 HDL-C（高密度脂蛋白胆固醇）和甘油三酯浓度之间的关联

背景：ChREBP（碳水化合物反应元件结合蛋白）是一种对糖消耗作出反应的转录因子。CHREBP基因座中的含糖饮料 (SSB) 消费和遗传变异分别与 HDL-C（高密度脂蛋白胆固醇）和甘油三酯浓度相关。我们假设 SSB 消费会改变CHREBP中遗传变异之间的关联基因座和血脂异常。方法：来自基因组流行病学联盟（N = 63 599）和英国生物库（N = 59 220）的心脏和衰老研究队列的 11 个队列的数据用于量化 SSB 消耗、遗传变异、以及它们使用线性回归模型对 HDL-C 和甘油三酯浓度的相互作用。总共考虑了CHREBP内或附近的 1606 个单核苷酸多态性。SSB 消费量是根据经过验证的问卷估计的，参与者按他们的估计摄入量分组。结果：在一项荟萃分析中，rs71556729 仅在最高 SSB 消费者中与较高的 HDL-C 浓度显着相关（β，2.12 [95% CI， 1.16–3.07] mg/dL 每个等位基因；P<0.0001），但在最低 SSB 消费者中并不显着（P = 0.81；P _Diff <0.0001）。对于另外 2 个变体（rs35709627 和 rs71556736）也观察到了类似的结果。对于甘油三酯，rs55673514 仅在最高 SSB 消费者中与甘油三酯浓度呈正相关（β，0.06 [95% CI，0.02-0.09] ln-mg/dL 每个等位基因，P = 0.001），但与最低 SSB 消费者无关（P = 0.84；P _Diff =0.0005)。结论：我们的结果确定了CHREBP中的遗传变异位点可以防止与 SSB 相关的 HDL-C 降低和其他可能加剧 SSB 相关甘油三酯浓度升高的变体。注册：URL：https://www.clinicaltrials.gov；唯一标识：NCT00005133、NCT00005121、NCT00005487、NCT00000479。

更新日期：2021-08-17

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