Can Leisure-Time Physical Activity Help Offset Genetic Risk?

As interest in personalized health grows, understanding the interplay between genetics and lifestyle becomes increasingly important. This study offers new insights into physical activity and cardiovascular risk.
Can Leisure-Time Physical Activity Help Offset Genetic Risk?
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Springer International Publishing
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Leisure-time physical activity is associated with lower cardiovascular risk in carriers of the rs693 (APOB) and rs1799983 (NOS3) polymorphisms: a cross-sectional study - Nutrire

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide, especially in low- and middle-income countries. To analyze the interaction between the rs693 (APOB gene) and rs1799983 (NOS3 gene) polymorphisms and leisure-time physical activity (LTPA) and cardiovascular risk (CVR) in adults. This population-based cross-sectional household study in Brazil evaluated CVR using the Framingham Risk Score (FRS), categorized as low (< 5%) or intermediate-to-high (≥ 5%). LTPA was self-reported via a VIGITEL-based questionnaire and categorized per current guidelines. The rs693 and rs1799983 polymorphisms were genotyped by real-time polymerase chain reaction with TaqMan® probes and classified as wild-type homozygous (TT and TT), heterozygous (CT and GT), and mutant homozygous (CC and GG), respectively. A combined genetic risk score was created, in which each genotype received a score from 0 to 2 according to the number of risk alleles. The values were summed, weighted by coefficients estimated in the sample, and subsequently categorized as low or high risk according to the median. Associations between genotypes, LTPA, and CVR were analyzed using univariate and multivariate logistic regression. Among 1,532 participants, 50.6% were male, 46.7% were aged 35–59 years, and 70.3% were physically inactive. Homozygosity for the variant allele was observed in 15.7% of participants for the rs693 polymorphism (CC) and 10.4% for the rs1799983 polymorphism (GG). Physically active individuals with the rs693 variant allele had a lower likelihood of elevated CVR (OR = 0.2; 95% CI: 0.1–0.7; p = 0.007) compared to wild-type homozygotes who were physically inactive. For rs1799983, wild-type homozygous and physically inactive individuals had a higher likelihood of elevated CVR (OR = 2.2; 95% CI: 1.2–3.9; p = 0.011) than physically active individuals with the same genotype. In crude analysis, individuals with high genetic risk but who were physically active had a lower likelihood of elevated CVR (OR = 0.5; 95% CI: 0.2–0.9; p = 0.025) than the low genetic risk and physically active group. Thus, leisure-time physical activity modified the association between rs693 and rs1799983 polymorphisms and CVR, indicating a significant interaction between genetic factors and lifestyle.

Cardiovascular diseases continue to be a major global health concern, accounting for a substantial burden of illness and mortality across countries and populations. While the importance of physical activity for cardiovascular health is well established, researchers are increasingly interested in understanding how lifestyle factors interact with genetic variation to influence disease risk.

A recent study published in  Nutrire contributes to this discussion by examining the relationship between leisure-time physical activity and cardiovascular risk in individuals carrying specific variants of the APOB and NOS3 genes. Both genes have been widely studied because of their involvement in biological pathways related to lipid metabolism and vascular function, two key components of cardiovascular health.

Using a cross-sectional design, the authors explored whether the association between physical activity and cardiovascular risk differed according to genetic background. Their findings suggest that leisure-time physical activity was associated with a lower cardiovascular risk among carriers of the rs693 variant in the APOB gene and the rs1799983 variant in the NOS3 gene.

Genes x lifestyle
The study is particularly interesting because it moves beyond the often simplified debate of “genes versus lifestyle.” Instead, it highlights the possibility that health outcomes may emerge from the interaction between biological predisposition and everyday behaviors. This perspective is becoming increasingly relevant as researchers seek more nuanced approaches to disease prevention and health promotion.

The findings should be interpreted within the context of the study design, which does not allow conclusions about cause and effect. Even so, the work adds valuable evidence to the broader literature showing that regular physical activity remains an important component of cardiovascular health and may be beneficial across different genetic profiles.

For researchers working in nutrition, public health, exercise science, genetics, and preventive medicine, this article offers an opportunity to reflect on how lifestyle interventions and genetic factors can be considered together. As interest in personalized approaches to health continues to grow, studies such as this help build a more detailed understanding of the many influences that contribute to cardiovascular risk.

Author's note: I used Microsoft Copilot to assist in creating this post.
Image: Jonathan Billinger/Wikimedia Commons

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Go to the profile of Olena Yelizarova
about 3 hours ago

I also really like this shift from ‘genes versus lifestyle’ to ‘genes × lifestyle’. To me, this is much closer to how risk actually emerges in real populations: genetic background does not operate in isolation, but through its interaction with behavior and environment. That move away from genetic determinism toward a more dynamic, context-dependent view of risk is especially valuable.

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