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The adiponectin gene SNP+276G>T associates with early-onset coronary artery disease and with lower levels of adiponectin in younger coronary artery disease patients (age ≤50 years)

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Abstract

Adiponectin, an adipocyte-derived protein, is an essential modulator of insulin sensitivity and several studies suggest an important role of adiponectin in the processes leading to atherosclerosis, thus indicating the adiponectin gene as a potential candidate for coronary artery disease (CAD). In the present study we have studied the association between two single nucleotide polymorphisms (SNPs) (+45T>G and +276 G>T) of the adiponectin gene and CAD, looking also into the possible influence of these SNPs on adiponectin plasma levels. The SNPs were analysed in a first cohort of 595 subjects, 325 with CAD and 270 matched controls. We observed a significant association (p<0.001) between the SNP +276G>T in the adiponectin gene and CAD. In multivariate analysis, carriers of the +276G>T SNP had an odds ratio (OR) for CAD of 4.99 (p<0.0007). A strong interaction between the +276G>T SNP and age was also present (OR, 1.03; p<0.0001). The increase in CAD risk was most evident among individuals with early-onset CAD (age ≤50 years), whereas in older CAD subjects other factors, and not the adiponectin SNP, were the major determinants. Furthermore, in CAD subjects with early-onset disease this SNP was also a significant determinant of lower levels of serum adiponectin levels. This association resulted independent from the other variables known to be associated with CAD in our population, including sex, body mass index, high-density lipoprotein and Homeostasis Model Assessment for insulin resistance. To confirm the results the +276G>T SNP was analysed in a second cohort of CAD and controls. The difference between CAD and controls in the +276G>T SNP frequencies showed a similar trend as before, although not significant. The combination of the two cohorts (1,046 subjects: 580 CAD and 466 controls) showed a statistically significant association, particularly in CAD subjects with early-onset of disease. In addition, we confirmed that in younger CAD subjects the SNP was a significant determinant of lower levels of adiponectin. In view of these results, it could be speculated that the adiponectin gene variant, or a mutation in linkage with it, determines lower adiponectin gene expression, causing in turn an increased risk to develop insulin resistance, atherosclerosis and cardiovascular disease. The significant association of the adiponectin gene in subjects with early-onset CAD also suggests that that genetic factors for late-onset diseases may exert a greater influence in younger persons, when other risk factors are not as prevalent as in older age groups.

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Acknowledgements

Financial support to this work was provided by the Faculty of Medicine (grant C26F022871) of the University of Rome “La Sapienza”, by the Italian Ministry of the University and Scientific Research (COFIN 2003), and by the Ministry of Health (grant RF2003) all to M.G. Baroni. We wish to thank Dr. Paolo Rubino and Dr. Tullio Tesorio, Cardiac Catheterisation Unit, Casa di Cura Montevergine di Mercogliano (AV), for their participation in the study

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Authors and Affiliations

  1. Department of Clinical Sciences, Division of Endocrinology, Policlinico Umberto I, University of Rome La Sapienza, 00161, Rome, Italy

    Emanuela Filippi, Federica Sentinelli, Stefano Romeo, Claudio Tiberti, Antonella Verrienti, Marzia Fanelli, Mara Fallarino & Marco Giorgio Baroni

  2. Department of Medical Sciences, Faculty of Medicine, University of Cagliari, Italy

    Marco Giorgio Baroni

  3. Department of Medical Therapy, University of Rome La Sapienza, Rome, Italy

    Marcello Arca

  4. Department of Cardiology, II Faculty of Medicine, University of Rome La Sapienza, Rome, Italy

    Andrea Berni

  5. Cardiac Catheterisation Unit, Casa di Cura Montevergine di Mercogliano (Av), Mercogliano, AV, Italy

    Giovanni Sorropago

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  1. Emanuela Filippi
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Correspondence to Marco Giorgio Baroni.

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Filippi, E., Sentinelli, F., Romeo, S. et al. The adiponectin gene SNP+276G>T associates with early-onset coronary artery disease and with lower levels of adiponectin in younger coronary artery disease patients (age ≤50 years). J Mol Med 83, 711–719 (2005). https://doi.org/10.1007/s00109-005-0667-z

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