Associations Between Genetic Variants near the CHREBP Locus and Lipoprotein Concentrations May Be Modified by Sugar-Sweetened Beverage Consumption. (29th May 2020)

• Record Type: Journal Article
• Authors: Haslam, Danielle; Peloso, Gina; Smith, Caren; Dupuis, Josee; Dashti, Hassan; Lichtenstein, Alice; Herman, Mark; McKeown, Nicola
• Is Part Of: Current developments in nutrition. Volume 4(2020)Supplement 2
• Page Start: 1256
• Page End: 1256
• Publication Date: 2020-05-29
• Subjects: Nutrition -- Periodicals; Nutritional Physiological Phenomena; Nutrition; Periodicals; Periodicals; Fulltext; Internet Resources; Periodicals; 612.3
• DOI: 10.1093/cdn/nzaa058_014
• Languages: English
• ISSNs: 2475-2991

Abstract

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 ( p trend < 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; p interact = 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.