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• 作者：Emanuela Filippi ; Federica Sentinelli ; Stefano Romeo ; Marcello Arca ; Andrea Berni ; Claudio Tiberti ; Antonella Verrienti ; Marzia Fanelli ; Mara Fallarino and Giovanni Sorropago ; et al.
• 关键词：Adiponectin gene ; CAD ; HOMAIR ; Body mass index (BMI) ; Real ; time PCR ; Single nucleotide polymorphisms (SNPs)
• 刊名：Journal of Molecular Medicine
• 出版年：2005
• 出版时间：September 2005
• 年：2005
• 卷：83
• 期：9
• 页码：711-719
• 全文大小：174 KB

文摘

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 (p276G>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 (p276G>T SNP and age was also present (OR, 1.03; p50 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.