Gene-diet interactions and cardiovascular diseases: a systematic review of observational and clinical trials

Abstract

Background Both genetic background and diet are important determinants of cardiovascular diseases (CVD). Understanding gene-diet interactions could help improve CVD prevention and prognosis. We aimed to summarise the evidence on gene-diet interactions and CVD outcomes systematically. Methods We searched MEDLINE® via Ovid, Embase, PubMed®, and The Cochrane Library for relevant studies published until June 6th 2022. We considered for inclusion cross-sectional, case–control, prospective cohort, nested case–control, and case-cohort studies as well as randomised controlled trials that evaluated the interaction between genetic variants and/or genetic risk scores and food or diet intake on the risk of related outcomes, including myocardial infarction, coronary heart disease (CHD), stroke and CVD as a composite outcome. The PROSPERO protocol registration code is CRD42019147031. Results and discussion We included 59 articles based on data from 29 studies; six articles involved multiple studies, and seven did not report details of their source population. The median sample size of the articles was 2562 participants. Of the 59 articles, 21 (35.6%) were qualified as high quality, while the rest were intermediate or poor. Eleven (18.6%) articles adjusted for multiple comparisons, four (7.0%) attempted to replicate the findings, 18 (30.5%) were based on Han-Chinese ethnicity, and 29 (49.2%) did not present Minor Allele Frequency. Fifty different dietary exposures and 52 different genetic factors were investigated, with alcohol intake and ADH1C variants being the most examined. Of 266 investigated diet-gene interaction tests, 50 (18.8%) were statistically significant, including CETP-TaqIB and ADH1C variants, which interacted with alcohol intake on CHD risk. However, interactions effects were significant only in some articles and did not agree on the direction of effects. Moreover, most of the studies that reported significant interactions lacked replication. Overall, the evidence on gene-diet interactions on CVD is limited, and lack correction for multiple testing, replication and sample size consideration.

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“…Moreover, other studies used food frequency questionnaires with no information on whether they were tested for validity. Genotyping errors can also affect the results of gene-diet interactions by leading to deviations from the true genotype ( 172 , 173 ).…”

“…Nonetheless, most of the studies had small sample sizes and only a few included information on statistical power to detect interactions. There is also the risk of false-positive finding when there is no correction for multiple comparisons ( 173 , 175 ), but only a few of the studies provided information on correction for multiple comparisons.…”

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“…In the realm of precision preventive medicine, an ongoing area of exploration involves examining how particular dietary factors or dietary patterns may influence the genetic susceptibility to cardiovascular diseases. Although there have been significant enthusiasm and substantial investments in this area, a recent review indicates that the available evidence regarding gene-diet interactions in cardiovascular diseases is quite limited, suffering from many methodological limitations [28].…”

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“…Furthermore, clinical trials are currently underway to determine the possibility of controlling blood sugar levels based on personal microbiome information ( 12 , 13 ). Furthermore, investigations are being conducted to ascertain the statistical significance of the correlation among the genes, diet, and disease of an individual and to evaluate the efficacy of dietary interventions in disease prevention ( 14 , 15 ). In addition to lifestyle and eating habits, studies are underway to provide optimal personalized nutrition by analysing correlations based on data from individual intestinal microbes and discovering disease-related diagnostic indicators ( 16 ).…”