Genetic variants and expression study of FOXP3 gene in acute coronary syndrome in Iranian patients Milad Gholami 1 , Ali Esfandiary 1 , Masoumeh Vatanparast 2 , Reza Mirfakhraie 1 , Mir Mohsen Hosseini 3 and Soudeh Ghafouri-Fard 1 * 1 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2 Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 3 Department of Microbiology, Faculty of Basic and Medical Science, Islamic Azad University, Zanjan Branch, Zanjan, Iran Acute coronary syndrome (ACS) is the most serious form of coronary artery disease. Inflammatory processes participate in dif- ferent stages of this disorder. FOXP3 gene plays an important role for the development and function of regulatory T cells. Con- sequently, the expression level and polymorphisms of this gene have been studied in many immune related diseases. In the present study, we analysed the expression of FOXP3 as well as the association between two variants in this gene (rs3761548A/C and rs5902434del/ATT) and occurrence of ACS in Iranian patients. FOXP3 expression analysis showed a sig- nificant decrease in patients with ACS compared with controls (P = 0.029). In addition, a significant decrease has been detected in female patients compared with normal female subjects (P = 0.020). No significant change has been observed in FOXP3 ex- pression in male patients compared with normal male subjects. In addition, no difference has been detected between ACS and normal subjects in combined genotype frequencies of both polymorphisms and the allele frequencies of rs5902434. However, rs3761548 C allele was more prevalent in controls compared with patients with ACS (P = 0.024). Consequently, our data dem- onstrated that FOXP3 expression is markedly decreased in female patients with ACS, which highlight the role of immune re- sponses in plaque destabilization in such patients. Copyright © 2016 John Wiley & Sons, Ltd. SIGNIFICANCE PARAGRAPH Considering the role of immune system in different stages of acute coronary syndrome (ACS), we evaluated the expression of FOXP3 gene as a master regulator of immune response in these patients compared with normal subjects. We detected a significant down-regulation of this gene in patients with ACS. Such decreased expression was more prominent in female patients, which implies the role of immune responses in plaque destabilization in such patients. key words—acute coronary syndrome; FOXP3; polymorphism; expression INTRODUCTION Cardiovascular disease is the leading cause of death world- wide, responsible for 17.3 million deaths annually. Such number is predicted to increase to more than 23.6 million by 2030. 1 Acute coronary syndrome (ACS) is among the most terrible and catastrophic of acute cardiac disorders, accounting for a high number of such annual global mortality. 2 The under- lying pathology of ACS is believed to be plaque rupture or erosion with overlying thrombosis. Inflammation is considered to be a culprit in plaque disruption, although the stimuli that activate the acute inflammatory process remain subtle. 3 As up-regulation of T helper (Th)1 response has been shown in both the atherosclerotic lesions and circulating lymphocytes of patients with ACS, it has been deduced that Th1/Th2 imbal- ance participates in plaque rupture and the onset of ACS. 4 In addition, since an anti-inflammatory role has been assigned for CD4 + CD25+ regulatory T (Treg) cells, recent studies have suggested a critical role for these cells in pathogenesis of ACS. 5 These cells have been shown to express the forkhead/winged helix transcription factor (Foxp3) and partic- ipate in maintenance of tolerance to self components by contact-dependent suppression or releasing anti-inflammatory cytokines. 6 Consequently, FOXP3 gene polymorphisms have been shown to be linked to several inflammatory disorders including systemic lupus erythematosus (SLE), autoimmune thyroid diseases, type I diabetes, allergic rhinitis and unex- plained recurrent spontaneous abortion. 7 In addition, the single nucleotide polymorphism rs3761548 of FOXP3 gene has been recently shown to be associated with ACS in Chinese Han population. 8 In this study, we evaluated the association between two functional polymorphisms *Correspondence to: Soudeh Ghafouri-Fard, Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. E-mail: s.ghafourifard@sbmu.ac.ir Received 21 December 2015 Revised 31 January 2016 Accepted 5 February 2016 Copyright © 2016 John Wiley & Sons, Ltd. cell biochemistry and function Cell Biochem Funct 2016; 34: 158–162. Published online 29 February 2016 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/cbf.3174