ABC | Volume 110, Nº1, January 2018

Original Article Association of Multiple Genetic Variants with the Extension and Severity of Coronary Artery Disease Simone Cristina Pinto Matheus Fischer, Simone Pires Pinto, Lívia Campos do Amaral Silva Lins, Henrique Tria Bianco, Carlos Manoel de Castro Monteiro, Luiz Fernando Muniz Pinheiro, Francisco Antonio Helfenstein Fonseca, Maria Cristina de Oliveira Izar Universidade Federal de São Paulo (UNIFESP), São Paulo, SP – Brazil Mailing Address: Maria Cristina de Oliveira Izar • Alameda das Dracenas, 290. Postal Code 06539-240, Alphaville 5, Santana de Parnaíba, SP – Brazil E-mail: mcoizar@cardiol.br , mcoizar@terra.com.br Manuscript received May 13, 2017, revised manuscript July 11, 2017, accepte August 02, 2017 DOI: 10.5935/abc.20170177 Abstract Background: Metabolic syndrome (MS) is a condition that, when associatedwith ischemic heart disease and cardiovascular events, can be influenced by genetic variants and determine more severe coronary atherosclerosis. Objectives: To examine the contribution of genetic polymorphisms to the extension and severity of coronary disease in subjects with MS and recent acute coronary syndrome (ACS). Methods: Patients (n = 116, 68% males) aged 56 (9) years, with criteria for MS, were prospectively enrolled to the study during the hospitalization period after an ACS. Clinical and laboratory parameters, high-sensitivity C-reactive protein, thiobarbituric acid reactive substances, adiponectin, endothelial function, and the Gensini score were assessed. Polymorphisms of paraoxonase-1 (PON-1), methylenotetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (ENOS), angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT1R), apolipoprotein C3 (APOC3), lipoprotein lipase (LPL) were analysed by polymerase chain reaction (PCR) technique, followed by the identification of restriction fragment length polymorphisms (RFLP, and a genetic score was calculated. Parametric and non-parametric tests were used, as appropriate. Significance was set at p < 0.05. Results: Polymorphisms of PON-1, MTHFR and ENOS were not in the Hardy-Weinberg equilibrium. The DD genotype of LPL was associated with higher severity and greater extension of coronary lesions. Genetic score tended to be higher in patients with Gensini score < P50 (13.7 ± 1.5 vs. 13.0 ± 1.6, p = 0.066), with an inverse correlation between genetic and Gensini scores (R = –0.194, p = 0.078). Conclusions: The LPL polymorphism contributed to the severity of coronary disease in patients with MS and recent ACS. Combined polymorphisms were associated with the extension of coronary disease, and the lower the genetic score the more severe the disease. (Arq Bras Cardiol. 2018; 110(1):16-23) Keywords: Coronary Artery Disease / genetic; Polymorphism, Genetic; Metabolic Syndrome; Sedentary Lifestyle. Introduction Ischemic heart disease and stroke account for the majority of deaths in the world. 1 With progressive urbanization, adoption of a sedentary lifestyle and better access to packaged food, increasing incidence of obesity and overweight has been observed in the population, 2 accompanied by an increase in metabolic disorders and cardiovascular risks. The concept of metabolic syndrome (MS) was first described by Reaven, as a relationship between insulin resistance, arterial hypertension, lipid abnormalities and visceral obesity. 3,4 MS has been associated with higher rates of fatal and non-fatal cardiovascular events. 5,6 Its high prevalence in acute coronary syndrome (ACS) has also been associated with greater anatomical obstruction. 7 Our group showed that patients with MS and ACS had lower insulin sensitivity, severe coronary artery disease (CAD) associated with high levels of C-reactive protein (CRP) and low IgG antibody titers to oxidized low-density lipoprotein, 8-10 associated with greater extension of CAD. 11 Some studies have explored the association of genetic variants with cardiovascular outcomes. 12-16 Large Mendelian randomization studies have allowed the understanding of the effects of some clinical parameters throughout life, such as LDL-c, HDL-c and triglycerides on cardiovascular risk, as well as the protective effect of polymorphisms associated with lower systolic blood pressure. 17-19 Although hypothetical, the effects of polymorphisms have been associated with the extension and severity of CAD. 20-22 Smaller studies, systematic review and meta-analyses have proposed genetic variants associated with CAD, as well as genetic scores to identify individuals at higher cardiovascular risk, 23-25 since many genetic variants with only modest individual effect may have a larger impact when a greater 16