Interleukin-18 gene promoter polymorphisms and recurrent spontaneous abortion Sirous Naeimi a , Alireza Fotouhi Ghiam a , Zahra Mojtahedi a , Alamtaj Samsami Dehaghani b , Dawar Amani c , Abbas Ghaderi a,c, * a Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran b Department of Obstetric and Gynecology, Shiraz University of Medical Sciences, Shiraz, Iran c Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran Received 26 July 2005; received in revised form 9 January 2006; accepted 8 February 2006 Abstract Background: IL-18 is a multifunctional cytokine capable of inducing either Th1 or Th2 polarization depending on the immunologic milieu. IL-18 is detected at the materno-fetal interface very soon in early pregnancy. Two polymorphisms in the promoter region of the IL-18 gene at positions of À607 and À137 appear to have functional impacts. Objective: This study attempts to evaluate the frequency of these two polymorphisms in the IL-18 gene promoter in patients with recurrent spontaneous abortion (RSA) and normal pregnant women. Subjects and methods: One hundred and two RSA patients and 103 healthy pregnant women were enrolled in this study. Single nucleotide polymorphisms of the IL-18 gene at positions À607 (C/A) and À137 (G/C) were analyzed by the sequence-specific PCR method. Results: There was no significant association between the allele, genotype, and haplotype frequencies of the two single nucleotide polymorphisms (SNPs) in the IL-18 gene promoter and RSA. Conclusion: The results of this study showed that IL-18 gene promoter polymorphisms at positions À607 and À137 did not confer susceptibility to RSA in southern Iranian patients. # 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Interleukin-18; Polymorphism; Recurrent spontaneous abortion 1. Introduction Recurrent spontaneous abortion (RSA), the occurrence of three or more consecutive pregnancy losses in the first trimester, occurs in approximately 1% of pregnant women worldwide. A series of etiological factors responsible for RSA are divided into the embryologically driven causes (abnormal embryonic karyotypes) and maternally driven ones affecting the endometrium and/or placenta (luteal phase defect, hyperprolactinemia, hyperhomocysteinemia, uterine anomalies, coagulation disorders, autoimmune diseases, endocrine disorders, and endometrial defects) [1]. Despite these well-established pathophysiological mechanisms, the exact underlying etiology is still poorly understood in up to 50% of RSA cases. Recent studies shed light on the immune mechanism as a cause of a proportion of these idiopathic pregnancy losses [1–4]. Production of cytokines and the distribution of the immune cells during pregnancy appeared to be critical in pregnancy outcome [1–4]. Interleukin (IL)-18, initially known as an interferon (IFN)-g inducing factor, is a member of the IL-1 cytokine family, which is produced by a variety of immune and non-immune cells. It is a unique cytokine capable of enhancing either Th1 or Th2 differentiation depending on the immunologic milieu. It also augments the cytotoxic actions of natural killer and CD8+ T cells [5,6]. www.elsevier.com/locate/ejogrb European Journal of Obstetrics & Gynecology and Reproductive Biology 128 (2006) 5–9 * Corresponding author at: Shiraz Institute for Cancer Research, P.O. Box: 71345-1798, Shiraz, Iran. Tel.: +98 711 230 3687; fax: +98 711 230 4952. E-mail address: ghaderia@sums.ac.ir (A. Ghaderi). 0301-2115/$ – see front matter # 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2006.02.012