Research Article Replication of GWAS Coding SNPs Implicates MMEL1 as a Potential Susceptibility Locus among Saudi Arabian Celiac Disease Patients Omar I. Saadah, 1,2 Noor Ahmad Shaik, 3 Babajan Banaganapalli, 2 Mohammed A. Salama, 2,4 Sameer E. Al-Harthi, 2,5 Jun Wang, 2,6 Harbi A. Shawoosh, 7 Sharifa A. Alghamdi, 8 Yagoub Y. Bin-Taleb, 1 Bakr H. Alhussaini, 1 Ramu Elango, 2 and Jumana Y. Al-Aama 2,3 1 Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia 2 Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia 3 Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia 4 Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia 5 Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia 6 BGI, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China 7 Department of Pediatrics, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia 8 Department of Pediatrics, Division of Gastroenterology, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia Correspondence should be addressed to Jumana Y. Al-Aama; jalama@kau.edu.sa Received 25 August 2015; Accepted 16 November 2015 Academic Editor: George Perry Copyright © 2015 Omar I. Saadah et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Celiac disease (CD), a gluten intolerance disorder, was implicated to have 57 genetic susceptibility loci for Europeans but not for culturally and geographically distinct ethnic populations like Saudi Arabian CD patients. Terefore, we genotyped Saudi CD patients and healthy controls for three polymorphisms, that is, Phe196Ser in IRAK1, Trp262Arg in SH2B3, and Met518Tr in MMEL1 genes. Single locus analysis identifed that carriers of the 518 Tr/Tr (MMEL1) genotype conferred a 1.6-fold increased disease risk compared to the noncarriers (OR = 2.6; 95% CI: 1.22–5.54;  < 0.01). Tis signifcance persisted even under allelic (OR = 1.55; 95% CI: 1.05–2.28;  = 0.02) and additive (OR = 0.35; 95% CI: 0.17–0.71;  = 0.03) genetic models. However, frequencies for Trp262Arg (SH2B3) and Phe196Ser (IRAK1) polymorphisms were not signifcantly diferent between patients and controls. Te overall best MDR model included Met518Tr and Trp262Arg polymorphisms, with a maximal testing accuracy of 64.1% and a maximal cross-validation consistency of 10 out of 10 ( = 0.0156). Allelic distribution of the 518 Tr/Tr polymorphism in MMEL1 primarily suggests its independent and synergistic contribution towards CD susceptibility among Saudi patients. Lack of signifcant association of IRAK and SH2B3 gene polymorphisms in Saudi patients but their association in European groups suggests the genetic heterogeneity of CD. 1. Introduction Celiac disease (CD) is a T-cell-mediated infammatory dis- order with underlying involvement of autoimmune, genetic, and environmental components [1, 2]. Tis chronic enteropa- thy is caused by permanent intolerance to ingested gluten from wheat, barley, and rye in genetically susceptible chil- dren and adults [3–5]. Te common clinical manifestations presented by patients with CD are chronic diarrhea, abdom- inal distension, failure to thrive, and short stature [4, 6]. An approximate 1% prevalence rate of CD among Cau- casians places them as the most vulnerable ethnic group for developing CD. However, current day improved knowledge about celiac disease prevalence and clinical and diagnostic characteristics has indicated that it is common not only in Europe, but also in developing countries where wheat is Hindawi Publishing Corporation Disease Markers Volume 2015, Article ID 351673, 6 pages http://dx.doi.org/10.1155/2015/351673