Contribution of JAK2 and STAT3 variants to the genetic susceptibility of recurrent miscarriage among Bahraini and Tunisian Arabs Safia Messoudi • Manar A. Al-Sulaiti • Amna S. Al-Busaidi • Maryam Dendana • Brahim Nsiri • Wassim Y. Almawi • Touhami Mahjoub Received: 9 May 2012 / Accepted: 3 October 2012 / Published online: 14 October 2012 Ó Springer Science+Business Media Dordrecht 2012 Abstract We investigated the contribution of JAK2 rs2203724 and STAT3 rs1053023 and rs1053004 to the susceptibility of idiopathic recurrent miscarriage (IRM) in Bahraini (246 cases and 279 controls) and Tunisian (235 cases and 235 controls) Arabs. The distribution of JAK2 rs2203724 and STAT3 rs1053023 genotypes were in Hardy–Weinberg equilibrium (HWE) in both communities, while mild deviation from HWE was noted for rs1053004 in Tunisians but not Bahraini. JAK2 rs2203724 was not associated with IRM in either community, while STAT3 rs1053023 was positively associated with IRM in both Bahraini and Tunisian women. STAT3 rs1053004 displayed mixed association: it was positively associated with IRM in Bahraini (P \ 0.001), but not Tunisian women (P = 0.10). Genotype association confirmed the association of both STAT3 variants with IRM under additive, dominant, and recessive models, while the association of STAT3 rs1053023 was seen under additive and dominant, but not recessive models in Tunisians. The contribution of JAK2 and STAT3 variants to IRM susceptibility must be evalu- ated regarding specific variants, and the ethnic/racial background. Keywords Genotype Á JAK2 Á Polymorphisms Á Recurrent miscarriage Á STAT3 Introduction Idiopathic recurrent miscarriage (IRM) is a common reproductive problem [1]. While several causes were identified, most IRM cases are unexplained [2, 3], and an immunological basis was suggested [4]. Antigen-specific T cell activation converges at stimulation of Janus family tyrosine kinases (JAK) and signal transducers and activa- tors of transcription (STAT) family of intracellular medi- ators [5]. These were involved in inflammation, apoptosis, cell cycle control and development [6]. Four JAK (JAK1, JAK2, JAK3 and Tyk2), and seven STAT (STAT1, 2, 3, 4, 5a, 5b, 6) proteins were identified [7], which differ in receptor affinities [8]. Engagement of JAKs results in auto- phosphorylation and phosphorylation of STAT proteins, followed by homo- and hetero-dimerization of STATs and their nuclear translocation, where they bind specific DNA response elements, resulting in enhancement of the tran- scription of target genes [8]. Janus family tyrosine kinases–signal transducers and activators of transcription signaling pathway plays an important role in trophoblast invasion and differentiation, and is required for establishment and maintenance of preg- nancy [9]. The effect of IL-11 on normal placentation involves optimal decidua JAK2/STAT3 activity [10], and defective JAK2/STAT3 activity was implicated with adverse pregnancy outcomes [11–13], and embryonic lethality [11]. The expression of JAK and STAT proteins is genetically determined, and dysregulated STAT3 expres- sion and activation is associated with defective placentation [14, 15]. The association of JAK2 and STAT3 gene variants with IRM was explored, but with inconclusive findings [16–18]. In this study, we investigated the association of JAK2 and STAT3 variants with IRM risk in Bahraini (Arabian Peninsula) and Tunisian (North Africa) Arabs. S. Messoudi Á M. Dendana Á B. Nsiri Á T. Mahjoub Research Unit of Hematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia M. A. Al-Sulaiti Á A. S. Al-Busaidi Á W. Y. Almawi (&) Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, P.O. Box 22979, Manama, Bahrain e-mail: wassim@agu.edu.bh 123 Mol Biol Rep (2013) 40:585–589 DOI 10.1007/s11033-012-2096-8