The Interleukin 6 -572 G>C (rs1800796) Polymorphism Is Associated with the Risk of Developing Acute Coronary Syndrome Jose ´ Manuel Fragoso, 1,2 Hilda Delgadillo, 3 Teresa Jua ´ rez-Cedillo, 4 Jose ´ Manuel Rodrı ´guez-Pe ´ rez, 1 Maite Vallejo, 5 Oscar Pe ´ rez-Me ´ ndez, 1 Edith A ´ lvarez-Leo ´ n, 1 Marco Antonio Pen ˜ a-Duque, 3 Marco Antonio Martı ´nez-Rı ´os, 3 and Gilberto Vargas-Alarco ´n 1 Background: Inflammation plays an essential role in the development and progression of atherosclerotic lesions and plaque disruption. Cytokines are central regulators in immunoinflammatory mechanisms. The aim of the present study was to evaluate the role of INF-g and IL-6 gene polymorphisms as susceptibility markers for acute coronary syndromes (ACS) in a group of Mexican patients. Methods: Four polymorphisms (INF-g -155 G>A, INF-g -179 T>G, IL-6 -572 G>C, and IL-6 -1426 T>G) of the INF-g and IL-6 genes were analyzed by 5 0 exonuclease TaqMan genotyping assays in a group of 284 patients with ACS (mean age ¼ 58.88  11.7 years) and 247 healthy unrelated controls (mean age ¼ 56.03  4.13 years). Results: Distribution of INF-g -179 G>T (rs2069709) and INF-g -155 G>A (rs2069710) polymorphisms was similar in patients and healthy controls. A significant difference was observed in the distribution of IL-6 -572 G>C (rs1800796) genotypes between patients with ACS and healthy controls ( p ¼ 0.019). Estimated odds ratio and 95% confidence interval (CI) showed a protective role of the IL-6 -572 (rs1800796) CC when compared with the GG genotype (wild type) (odds ratio ¼ 0.6, 95% CI ¼ 0.33–1.08). In this case, heterozygous individuals with GC genotype had 2.19-fold increased risk of developing ACS than CC homozygous ( p ¼ 0.007, 95% CI ¼ 1.24–3.96). Conclusions: The results suggest that IL-6 -572 G>C (rs1800796) polymorphism could be involved in the risk of developing ACS in Mexican individuals. Introduction C oronary atherosclerosis is a complex multifactorial process resulting from an excessive inflammatory re- sponse to various forms of injurious stimuli to the arterial wall (Ross, 1999; Garcia-Moll, 2005; Fragoso et al., 2009). The in- flammatory processes, coupled with dyslipidemia, advanced glycation, and infectious agents play an important role in the progression of atherosclerotic plaque (Libby, 2002; Virmani et al., 2005). The transition of a stable coronary atherosclerotic lesion into a ruptured plaque, with subsequent thrombus formation, results in the clinical manifestation of an acute coronary syndrome (ACS) (Achar et al., 2005; Mouco et al., 2005; Ma ¨ larstig et al., 2006; Fragoso et al., 2009). Several cytokines have been associated with the development and severity of coronary diseases (Aukrust et al., 2008). Interferon- gamma (INF-g) plays a central role in the immune and in- flammatory response to a wide range of stimuli (Angerio, 2009). Also, it is a cytokine essential in the development and propagation of T helper 1 type immune response and is an important mediator of innate immunity. In addition, it acti- vates monocytes and macrophages, which when taking part in inflammatory responses produce free radicals and pro- inflammatory cytokines such as interleukin-6 (IL-6). IL-6 is a pleiotropic cytokine with a broad range of humoral and cel- lular immune effects relating to inflammation, host defense, and tissue injury (Abeywardena et al., 2009; Dienz and Rin- con, 2009; Fonseca et al., 2009). Several studies correlate the plasma levels of INF-g and IL-6 with the instability of the atherosclerotic plaque (Ridker et al., 2000; Wang et al., 2004; Heinisch et al., 2005; Tanaka et al., 2005; Pasqui et al., 2006). INF-g presents two single-nucleotide polymorphisms (SNPs) in the promoter region -179 G>T (rs2069709) and -155 G>A (rs2069710), which are associated with an increased expres- sion of INF-g in several diseases (Bream et al., 2002; Koch et al., 2005; Qi et al., 2005; Huang et al., 2007). On the other hand, two 1 Department of Molecular Biology and Cardiovascular Disease’s Genomic and Proteomic Study Group, Instituto Nacional de Cardiologı ´a Ignacio Cha ´vez, Mexico City, Mexico. 2 Postgrad in Biological Sciences, Universidad Nacional Auto ´noma de Me ´xico, Mexico City, Mexico. 3 Department of Interventional Cardiology, Instituto Nacional de Cardiologı ´a Ignacio Cha ´vez, Mexico City, Mexico. 4 Epidemiologic and Health Service Research Unit, Aging Area, Instituto Mexicano del Seguro Social, Mexico City, Mexico. 5 Sociomedical Department, Instituto Nacional de Cardiologı ´a Ignacio Cha ´vez, Mexico City, Mexico. GENETIC TESTING AND MOLECULAR BIOMARKERS Volume 14, Number 6, 2010 ª Mary Ann Liebert, Inc. Pp. 759–763 DOI: 10.1089/gtmb.2010.0001 759