Sugar‐Sweetened Beverage Intake as a Modulator of Genetic Associations for Chronic Inflammation Relevant to Cardiovascular Disease

Abstract

BackgroundCardiovascular diseases are the leading cause of death worldwide. Although much research has been devoted to understanding environmental and genetic sources of cardiovascular disease risk separately, little is known about how environmental exposures might modify genetic components of risk. The consumption of sugar‐sweetened beverages (SSBs) is one such environmental exposure that has been linked to elevated risk of cardiovascular outcomes. Although the underlying mechanisms are not fully understood, chronic inflammation is one of the most robust proposals for the elevated risk observed. Chronic inflammation is known to be affected by both genetic and environmental factors, but very few interaction effects between genetic risk of inflammation and SSB consumption have been defined.MethodsThis study analyzed cross‐sectional data from 1,043 adults in the Framingham Offspring Study cohort for whom both environmental and genetic data were available. Data were collected in exams six (1995–1998) and seven (1998–2001). Multiple linear regression analysis was performed to assess how SSB intake might modify the risk of inflammation associated with each of 806 single nucleotide polymorphisms (SNPs) from 218 linkage disequilibrium (LD) blocks previously found to be co‐associated with cardiovascular disease and adiposity phenotypes. Inflammation was assessed via each of four serum inflammation biomarkers: C‐reactive protein (CRP), adiponectin, myeloperoxidase (MPO), and fibrinogen.ResultsAfter adjustment for multiple testing, SNPs from 38 LD blocks displayed significant interactions with SSB intake when CRP was the outcome. Of these, 25 LD blocks comprised SNPs that displayed significant interaction effects of a consistent pattern. These LD blocks were characterized by patterns of reduced risk (six of the 25 LD blocks) or elevated risk (19 of the 25 LD blocks). When fibrinogen was the outcome, SNPs from one LD block displayed significant interactions with SSB intake. This LD block comprised two SNPs, each of which displayed significant interaction effects in a pattern of elevated risk. The genetic markers of interest were then mapped to genes, some of which play known roles in inflammatory processes. No statistically significant interaction effects were observed between SSB intake and either adiponectin or MPO.ConclusionSeveral SNPs displaying statistically significant gene‐environment interaction effects on inflammation biomarkers, in particular CRP, have been identified. Replication studies in other populations are required to conclusively determine the role of SSBs in modifying the association between specific genetic variants and biomarkers of chronic inflammation, a known risk factor for cardiovascular disease.Support or Funding InformationU.S. Department of Agriculture, under agreement No. 8050‐51000‐ 098‐00D National Heart, Lung, and Blood Institute grant U01‐HL072524‐04 National Institutes of Health (5R21HL114238‐02)