Dataset Information

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.

ABSTRACT:

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.

SUBMITTER: Haslam DE

PROVIDER: S-EPMC8373451 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Abstract Objectives Carbohydrate responsive element binding protein (ChREBP) is a transcription factor that responds to sugar consumption. Consumption of sugar-sweetened beverages (SSB) and genetic variants at the CHREBP (also known as MLXIPL) locus have separately been linked to dyslipidemia. We hypothesized that SSB intake may modify the associations between CHREBP variants and HDL-C and TG concentrations. Methods We conducted a cross-sectional analysis of data from 11 Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium cohorts (N = 63,599). A total of 1606 single-nucleotide polymorphisms (SNPs) were selected within or near the CHREBP locus. SSB intake (sodas, fruit punches, lemonades, or other fruit drinks) was estimated from food-frequency questionnaires. Participants were grouped by five categories of SSB intake (ranging from < 1 serving/month to > 1 serving/day). Inverse-variance weighted fixed- and random-effect meta-analyses were used to quantify the following associations: 1) SSB consumption and HDL-C and TG concentrations; 2) selected SNPs and HDL-C and TG concentrations; and 3) interactions between SSB consumption and selected SNPs, and HDL-C and TG concentrations. Results were corrected for multiple testing to achieve a global p < 0.05. Results SSB intake was inversely associated with HDL-C and positively associated with TG concentrations (ptrend < 0.0001). We replicated previously observed GWAS associations between one distinct SNP on HDL-C (rs71556736) and two distinct SNPs (rs71556736 and rs13225660) on TG concentrations (Bonferroni-corrected P < 0.0001). Additionally, we identified two distinct novel SNP associations with TG concentrations (rs42124 and rs10245965). One distinct SNP displayed a statistically significant difference in effect size by category of SSB intake with HDL-C, where each additional minor allele at rs71556729 was significantly associated with HDL-C concentrations only among the highest SSB consumers [>1 serving/day: β (SE) = 4.47 (1.10) mg/dl, P = 5.0E-05; pinteract = 0.0001]. Additional SNPs displayed a suggestive difference in effect size for both HDL-C and TG concentrations. Conclusions Our results indicate that high SSB consumption may modify the association between genetic variants within or near the CHREBP locus and HDL-C and TG concentrations. Funding Sources NIH, AHA, USDA-ARS.

Project description:Abstract Objectives A meta-analysis of 11 CHARGE cohorts (N = 63,599) suggested that genetic variants within or near the CHREBP locus may modify the associations between sugar sweetened beverage (SSB) consumption and high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations. The study objective was to replicate these findings in a large independent cohort. Methods Blood lipids and 24-hour recalls were available for 57,794 adults of European ancestry in the UK Biobank (2006-‘10). SSBs included “squash” and “fizzy” drinks derived from a single 24-hr recall. A total of 875 SNPs within or near the CHREBP locus were identified and included in this analysis. Associations between these SNPs and HDL-C and TG concentrations were quantified among participants who did not report SSB consumption (non-consumers, n = 45,866), reported ≥0.5 servings/day of SSB (consumers, n = 11,928), and a subset of consumers who reported ≥2 servings/day of SSB (high consumers, n = 3742). Interaction between SSB and selected SNPs on HDL-C and TG concentrations was evaluated by examining the difference in beta coefficients between strata. Results were considered statistically significant at a Bonferroni-corrected pinteract < 0.0001 (0.05/499 effective tests). Results A significant interaction between SSB consumption and TBL2-rs71556729 on HDL-C concentration previously observed in the meta-analysis was replicated in UK Biobank. However, we observed a stronger interaction for a SNP in high linkage disequilibrium (R2 = 0.93) FZD9-rs34821369 (MAF = 0.03, pinteract = 8.2E-05) with TBL2-rs71556729 (MAF = 0.03, pinteract = 0.0004). Among only SSB consumers, each additional minor G allele at FZD9-rs34821369 was associated with mean HDL-C concentrations 1.63 mg/dL (SE = 0.53, P = 0.002) higher than those with the major T allele. Conclusions Our results suggest that adults with the minor allele at FZD9-rs34821369 may be protected against SSB-induced low HDL-C concentrations. These results are consistent the findings from a prior meta-analysis of 11 cohorts. Funding Sources NIH, AHA, USDA-ARS. This research has been conducted using the UK Biobank Resource (Application Number 35,835).

Project description:BackgroundProspective cohort studies have found a relation between sugar-sweetened beverage consumption (SSB; sodas and fruit drinks) and dyslipidemia. There is limited evidence linking SSB consumption to emerging features of dyslipidemia, which can be characterized by variation in lipoprotein particle size, remnant-like particle (RLP), and apolipoprotein concentrations.ObjectiveTo examine the association between SSB consumption and plasma lipoprotein cholesterol, apolipoprotein, and lipoprotein particle size concentrations among US adults.MethodsWe examined participants from the Framingham Offspring Study (FOS) (1987-1995; n = 3047) and the Women's Health Study (1992; n = 26,218). Plasma LDL-C, apolipoprotein (apo) B, HDL-C, apoA1, triglyceride (TG), non-HDL-C, total: HDL-cholesterol ratio, and apoB: apoA1 concentrations were quantified in both cohorts, and apoE, apoC3, RLP-TG, and RLP-cholesterol concentrations in FOS only. Lipoprotein particle sizes were calculated from NMR signals for lipoprotein particle subclass concentrations (triglyceride-rich lipoprotein particles [TRL-P; very large, large, medium, small, and very small], LDL-particles [LDL-P; large, medium, and small], HDL-particles [HDL-P; large, medium, and small]). SSB consumption was estimated from food frequency questionnaire data. We examined the associations between SSB consumption and all lipoprotein and apoprotein measures in linear regression models, adjusting for confounding factors, such as lifestyle, diet, and traditional lipoprotein risk factors.ResultsSSB consumption was positively associated with LDL-C, apoB, TG, RLP-TG, RLP-C, non-HDL-C concentrations and total: HDL cholesterol and apoB: apoA1 ratio, and negatively associated with HDL-C and apoA1 concentrations (P-trend ranges from < 0.0001 to 0.003). After adjustment for traditional lipoprotein risk factors, SSB consumers had smaller LDL-P and HDL-P sizes, lower concentrations of large LDL-P and medium HDL-P, and higher concentrations of small LDL-P, small HDL-P, and large TRL-P (P-trend ranges from < 0.0001 to 0.0009).ConclusionsHigher SSB consumption was associated with multiple emerging features of dyslipidemia that have been linked to higher cardiometabolic risk in US adults.