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

carotid intima-media thickness epidemiologic studies gene-environment interaction polymorphism, single nucleotide smoking

Journal

Circulation. Genomic and precision medicine
ISSN: 2574-8300
Titre abrégé: Circ Genom Precis Med
Pays: United States
ID NLM: 101714113

Informations de publication

Date de publication:
06 2023
Historique:
medline: 22 6 2023
pubmed: 7 4 2023
entrez: 6 4 2023
Statut: ppublish

Résumé

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. 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, 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. 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.

Sections du résumé

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.
METHODS
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,
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.

Identifiants

pubmed: 37021583
doi: 10.1161/CIRCGEN.122.003710
pmc: PMC10284137
doi:

Types de publication

Multicenter Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

236-247

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Auteurs

Buamina Maitusong (B)

Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China (B.M.).

Federica Laguzzi (F)

Unit of Cardiovascular & Nutritional Epidemiology, Institute of Environmental Medicine (F.L., U.d.F., K.L.), Karolinska Institutet, Stockholm, Sweden.

Rona J Strawbridge (RJ)

Cardiovascular Medicine Unit, Department of Medicine Solna (R.J.S., B.G.), Karolinska Institutet, Stockholm, Sweden.
Mental Health & Wellbeing, Institute of Mental Health & Wellbeing, University of Glasgow (R.J.S.).
Health Data Research, United Kingdom (R.J.S.).

Damiano Baldassarre (D)

Department of Medical Biotechnology & Translational Medicine, Università degli Studi di Milano (D.B.).
Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.).

Fabrizio Veglia (F)

Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.).

Steve E Humphries (SE)

Cardiovascular Genetics, Institute Cardiovascular Science, University College London, United Kingdom (S.E.H.).

Kai Savonen (K)

Foundation for Research in Health Exercise & Nutrition, Kuopio & Research Institute of Exercise Medicine, Kuopio, Finland (K.S.).
Department of Clinical Physiology & Nuclear Medicine, Kuopio University Hospital (K.S.).

Sudhir Kurl (S)

Institute of Public Health & Clinical Nutrition, University of Eastern Finland, Kuopio (S.K.).

Matteo Pirro (M)

Unit of Internal Medicine, Angiology & Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Italy (M.P.).

Andries J Smit (AJ)

Department of Medicine, University Medical Center Groningen, the Netherlands (A.J.S.).

Philippe Giral (P)

Unités de Prévention Cardiovasculaire, Assistance Publique-Hôpitaux de Paris, Service Endocrinologie-Métabolisme, Groupe Hospitalier Pitié-Salpétrière, France (P.G.).

Angela Silveira (A)

Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet & Karolinska Hospital, Stockholm, Sweden (A.S., A.H.).

Elena Tremoli (E)

Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.B., F.V., E.T.).

Anders Hamsten (A)

Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet & Karolinska Hospital, Stockholm, Sweden (A.S., A.H.).

Ulf de Faire (U)

Unit of Cardiovascular & Nutritional Epidemiology, Institute of Environmental Medicine (F.L., U.d.F., K.L.), Karolinska Institutet, Stockholm, Sweden.

Bruna Gigante (B)

Cardiovascular Medicine Unit, Department of Medicine Solna (R.J.S., B.G.), Karolinska Institutet, Stockholm, Sweden.

Karin Leander (K)

Unit of Cardiovascular & Nutritional Epidemiology, Institute of Environmental Medicine (F.L., U.d.F., K.L.), Karolinska Institutet, Stockholm, Sweden.

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