Lack of association between IL-1 and IL-6 gene polymorphisms and myocardial infarction in Turkish population A. Coker*, A. Arman†, O. Soylu‡, T. Tezel‡ & A. Yildirim‡ Summary Inflammation and genetics play a key role in the pathogenesis of atherosclerosis and its clinical result myocardial infarction (MI). Proinflammatory cytokines, IL-1 and IL-6, have been shown to play essential roles in developmental stages of coronary artery plaque forma- tion. The aim of this study was to determine the association between IL-1 [IL-1RN, IL-1b ()511, +3953)], IL-6 [)174, )572, )597] gene polymorphisms and MI in Turkish population. A total of 402 people were participated; 235 healthy control subjects and 167 MI patients (MI < 40, n: 72; MI > 40, n: 95). Polymer- ase chain reaction (PCR) was used to determine the genotype of IL-1RN, whereas the genotypes of IL-1b ()511, +3953) and IL-6 ()174, )572, )597) were determined using PCR followed with restriction diges- tion analysis. There was no significant difference between MI and controls for IL-1RN, IL-1b )511, +3953 (P: 0.875, 0.608, 0.442) and IL-6 )174, )572, )597 (P: 0.977, 0.632, 0.584) gene polymorphisms. Lack of association was observed between MI at younger age (MI < 40) and either IL-1RN VNTR, IL- 1b )511, +3953 (P: 0.878, 0.732, 0.978) or IL-6 )174, )572, )597 (P: 0.313, 0.654, 0.552) gene polymor- phisms. This study demonstrated that there was not any association between IL-1, IL-6 gene variants and MI in Turkish population. In addition, IL-1 and IL-6 gene polymorphisms did not affect MI at younger age (MI < 40) or older age (MI > 40). Thus, IL-1 and IL-6 single nucleotide polymorphisms may not be a risk factor for susceptibility to MI in Turkish population. Introduction Myocardial infarction (MI) is the rapid development of myocardial necrosis caused by a critical imbalance between oxygen supply and demand of the myocar- dium. The aetiology of MI is the interruption of blood supply to heart caused by atherosclerosis. Endothelial dysfunction is the first triggering stimuli of atheroscle- rosis and it is followed by foam cell, fatty streak, pla- que formation, rupture of plaque and thrombosis. Inflammatory cells and cytokines take major role dur- ing these processes. Pro-inflammatory cytokines such as IL-1 and IL-6 were shown to play a central role in the initiation and development of atherosclerosis (Ross, 1999). IL-1 family has two agonists (IL-1a and IL-1b) and one antagonist (Interleukin-1 Receptor antagonist:IL- 1Ra). IL-1b promotes inflammation by binding to the IL-1 Receptor Type I (IL-1RI), whereas IL-1Ra inhib- its IL-1-induced inflammation by binding to the IL-1 Receptor Type I (IL-1RI) (Auron, 1998). IL-1Ra and IL-1b, which are expressed from IL-1RN and IL-1b genes respectively, are highly polymorphic. There is a length variation within intron 2 caused by an 86-base pair variable number of tandem repeats (VNTR) in IL- 1RN gene (Steinkasserer et al., 1991; Tarlow et al., 1993; Vamvakopoulos et al., 2002). And also, single nucleotide polymorphisms (SNPs) were also previously determined at promoter position )511 C ⁄ T (dı Gıo- vıne et al., 1992) and in exon 5 at position +3953 C ⁄ T of IL-1 b gene (Pocıot et al., 1992). IL-6, which is proinflammatory cytokine, is expressed in lymphocytes, fibroblasts, monocytes and endothelial cells as response to cytokines such as IL-1 and TNF-a (Castell et al., 1989). It has a wide range of effects related to tissue injury, host defence and inflammation (Papanicolaou et al., 1998). Moreover, IL-6 is a central mediator of the acute phase response and hepatic production of C-reactive protein (CRP) (Heinrich et al., 1990). IL-6 is expressed from a gene located at chromosome 7 band p21 that coding 26 kDa molecular weight cytokine (Sehgal et al., 1986). Three SNPs were determined in the 5¢ flanking region of the IL-6 gene. One of these SNPs is the sub- stitution of Guanine residue to Cytosine at position * The Faculty of Science and Letters, Istanbul Kultur University, Istanbul, Turkey, † The Faculty of Engineering, Marmara University, Istanbul, Turkey and ‡ The Department of Cardiology, Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey Received 16 August 2010; revised 7 November 2010; accepted 23 November 2010 Correspondence: Ajda Coker, The Faculty of Science and Letters, The Department of Molecular Biology and Genetics, Atakoy Campus, Istanbul Kultur University, Istanbul 34156, Turkey. Tel: +90 212 498 45 67; Fax: +90 212 498 41 41; E-mail: a.coker@iku.edu.tr ª 2011 Blackwell Publishing Ltd, International Journal of Immunogenetics 38, 201–208 201 doi: 10.1111/j.1744-313X.2010.00988.x