Association of the STAT-6 rs324011 (C2892T) variant but not rs324015 (G2964A), with atopic asthma in a Saudi Arabian population Saleh Al-Muhsen a,b , Alejandro Vazquez-Tello a , Amer Jamhawi a , Hamdan Al-Jahdali c , Ahmed Bahammam d , Muslim Al Saadi b , Shaikh Mohammed Iqbal b , Abdulrahman Alfrayh b , Sibtain Afzal a , Nouf Al-Khamis b , Rabih Halwani a,b,⇑ a Prince Naif Center for Immunology Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia b Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia c King Saud University for Health Sciences, Riyadh, Saudi Arabia d Department of Internal Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia article info Article history: Received 3 July 2013 Accepted 29 May 2014 Available online 6 June 2014 Keywords: Atopic asthma IL-4 receptor STAT6 Case-control abstract Background: The signal transducer and activator of transcription 6 (STAT6) transduces signals in response to IL-4 and IL-13 cytokine stimulations, resulting in many cell-specific responses. Some common STAT6 SNPs were associated with asthma predisposition and/or IgE levels, although discrepancies have also been reported. Objective: To determine whether STAT6 rs324011 and rs324015 polymorphisms are associated with ato- pic asthma in Saudi Arabian patients. Methods: A total of 536 Saudi individuals aged 11–70 years old (230 atopic asthmatics, 306 healthy sub- jects) were recruited. DNA was purified from peripheral blood and genotyping for rs324011 and rs324015 polymorphisms was performed by PCR amplification, followed by cycle sequencing of the purified PCR fragments using BigDye chain terminator and capillary electrophoresis. Results: By the contrast of alleles tests, no significant differences between asthma and healthy groups were detected for both variants (rs324011: X 2 = 0.25, Pearson’s P-value = 0.617; rs324015: X 2 = 0.068, Pearson’s P = 0.814).When testing for genotypes, rs324011 homozygous T/T genotype was significantly associated with asthma, when the Recessive model is considered (T/T vs. C/C + C/T) (adjusted, OR = 2.49, 95% CI = 1.18–5.25, Pearson’s P = 0.014 / , Yates’ P = 0.022 / ). In contrast, rs324015 variant was not significantly associated with asthma. Conclusions: Rs324011 homozygous T/T genotype was significantly associated with asthma risk whereas rs324015 genotypes were not in the Saudi population. Ó 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. 1. Introduction The signal transducer and activator of transcription factor 6 (STAT6) is member of a family of 7 related proteins, which transmit extracellular signals perceived by a cell-surface receptor into the nucleus, where it drives the expression of target genes [1]. STAT6 is ubiquitously expressed, and is a critical mediator of IL-4 and IL-13 cytokine signaling, leading to many cell-specific responses, including the differentiation of Th2 lymphocytes and immunoglobulin E (IgE) production [2]. Through IL-4 and IL-13 activation, STAT6 also promotes allergic disorders such as food allergy, atopic asthma and atopic dermatitis [3]. Asthma is a chronic airway inflammatory disorder characterized by bronchial hyper-responsiveness and intermittent narrowing of small air- ways, with subsequent reversible airflow obstruction; STAT6 plays a prominent role in its pathogenesis, which is characterized by infiltration of predominantly Th2 cells, eosinophils, monocytes/ macrophages, mast cells, and elevated IL-4, IL-13 and IgE levels in the airways [4]. STAT6’s prominent role in asthma was demon- strated in knock-out STAT6 mice, which displayed reduction of Th2-related features and suppression of IgE [5,6]. Hence, STAT6 is http://dx.doi.org/10.1016/j.humimm.2014.05.012 0198-8859/Ó 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. ⇑ Corresponding author at: Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, P.O. Box 2925, 11461 Riyadh, Saudi Arabia. Fax: +966 1 4679463. E-mail address: rhalwani@ksu.edu.sa (R. Halwani). Human Immunology 75 (2014) 791–795 Contents lists available at ScienceDirect www.ashi-hla.org journal homepage: www.elsevier.com/locate/humimm