The role of genetic variation in apolipoprotein response to diet among Brazilians with cardiovascular disease

Abstract

Data on the interaction between dietary patterns, single nucleotide polymorphisms (SNPs), and cardiometabolic markers remain limited in genetically admixed populations, particularly among individuals with established cardiovascular disease (CVD). This study aimed to evaluate how SNPs modulate the effects of dietary interventions on apolipoprotein concentrations (A-I, A-II, B, C-II, C-III, and E) in Brazilians undergoing secondary cardiovascular prevention. This sub-study used data from the three-year multicenter BALANCE Trial, which enrolled individuals aged ≥40 with established CVD. Participants were assigned to either an intervention group (following the Brazilian Cardioprotective Diet with intensive monitoring) or a control group receiving general dietary advice. Apolipoproteins were measured via multiplex immunoassay, and SNPs were genotyped using the Axiom 2.0 Assay. GWAS and adjusted linear regression models assessed associations and gene-diet interactions related to apolipoproteins. A total of 266 participants (118 in the intervention group and 148 in the control group) were analyzed. After three years, significant SNP-diet interactions affecting log-transformed apolipoprotein concentrations were identified at a genome-wide significance threshold of 10⁻⁵. For each apolipoprotein evaluated, the following polymorphisms were associated: Apo A-I (rs11542163_T, rs11759163_T, rs13396579_C), Apo A-II (rs11197283_T, rs13185245_G, rs7666435_C), Apo B (rs13205819_G, rs926561_C), Apo C-II (rs143862519_TTC, rs674845_A, rs931606_G), Apo C-III (rs2247572_T, rs4506508_C, rs931606_G), and Apo E (rs4862401_G, rs6835179_G). Per-allele differences ranged from –0.65 mg/dL (Apo C-II, rs143862519_TTC) to +0.52 mg/dL (Apo B, rs13205819_G). Our findings show that genetic variants influence apolipoprotein responses to diet in Brazilians under secondary CVD prevention, supporting genotype-guided nutrition. NCT01620398.