Cross-Sectional Gene-Smoking Interaction Analysis in Relation to Subclinical Atherosclerosis-Results From the IMPROVE Study

Abstract

Background: Smoking is associated with carotid intima-media thickness (C-IMT). However, knowledge about how genetics may influence this association is limited. We aimed to perform nonhypothesis driven gene-smoking interaction analyses to identify potential genetic variants, among those included in immune and metabolic platforms, that may modify the effect of smoking on carotid intima-media thickness. Materials: We used baseline data from 1551 men and 1700 women, aged 55 to 79, included in a European multi-center study. Carotid intima-media thickness maximum, the maximum of values measured at different locations of the carotid tree, was dichotomized with cut point values ≥75, respectively. Genetic data were retrieved through use of the Illumina Cardio-Metabo- and Immuno- Chips. Gene-smoking interactions were evaluated through calculations of Synergy index (S). After adjustments for multiple testing, P values of <2.4×10 −7 for S were considered significant. The models were adjusted for age, sex, education, physical activity, type of diet, and population stratification. Results: Our screening of 207 586 SNPs available for analysis, resulted in the identification of 47 significant gene-smoking synergistic interactions in relation to carotid intima-media thickness maximum. Among the significant SNPs, 28 were in protein coding genes, 2 in noncoding RNA and the remaining 17 in intergenic regions. Conclusions: Through nonhypothesis-driven analyses of gene-smoking interactions, several significant results were observed. These may stimulate further research on the role of specific genes in the process that determines the effect of smoking habits on the development of carotid atherosclerosis.

Inflammation and endothelial function‐related gene polymorphisms are associated with carotid atherosclerosis—A study of community population in Southwest China

“…Smoking can promote the progression of systemic inflammation and promote the occurrence and development of atherosclerosis (Doran et al, 2003;Chang et al, 2014;Papagoras et al, 2014;Gulati et al, 2016;Rodríguez Huerta et al, 2016). Buamina et al found that there was an interaction between smoking and genes that may promote the development of carotid atherosclerosis (Maitusong et al, 2023). Reducing tobacco inhalation can reduce the incidence of carotid atherosclerosis.…”

“…Buamina et al. found that there was an interaction between smoking and genes that may promote the development of carotid atherosclerosis (Maitusong et al., 2023 ). Reducing tobacco inhalation can reduce the incidence of carotid atherosclerosis.…”

“…Genetic factors play an important role in the development of carotid atherosclerosis (Gardener et al., 2011 ; Grbić et al., 2022 ). Multiple risk factors may influence the relationship between the gene polymorphisms and carotid atherosclerosis (Li et al., 2022 ; Maitusong et al., 2023 ).…”

“…Genetic polymorphisms associated with inflammation and endothelial function may directly or indirectly interact with vascular risk factors to influence the onset and progression of atherosclerosis (Galkina & Ley, 2007 ; Gardener et al., 2011 ; Zhang et al., 2007 ). Previous studies have shown that multiple risk factors have an impact on the relationship between genes and carotid atherosclerosis, so it is necessary to analyze the correlation between genes and carotid atherosclerosis by combining multiple factors (Li et al., 2022 ; Maitusong et al., 2023 ).…”

Research advances in imaging markers for predicting hematoma expansion in intracerebral hemorrhage: a narrative review

“…For example, a study found that the combination of certain genetic variants and high blood pressure was associated with an increased risk of HE in ICH patients ( 30 ). Another study found that the interaction between genetic variants and smoking was associated with an increased risk of HE and poor outcomes in ICH patients ( 31 ).…”