title: Replication of GWAS Coding SNPs Implicates MMEL1 as a Potential Susceptibility Locus among Saudi Arabian Celiac Disease Patients.
abstract: 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. Therefore, we genotyped Saudi CD patients and healthy controls for three polymorphisms, that is, Phe196Ser in IRAK1, Trp262Arg in SH2B3, and Met518Thr in MMEL1 genes. Single locus analysis identified that carriers of the 518 Thr/Thr (MMEL1) genotype conferred a 1.6-fold increased disease risk compared to the noncarriers (OR = 2.6; 95% CI: 1.22-5.54; P < 0.01). This significance persisted even under allelic (OR = 1.55; 95% CI: 1.05-2.28; P = 0.02) and additive (OR = 0.35; 95% CI: 0.17-0.71; P = 0.03) genetic models. However, frequencies for Trp262Arg (SH2B3) and Phe196Ser (IRAK1) polymorphisms were not significantly different between patients and controls. The overall best MDR model included Met518Thr and Trp262Arg polymorphisms, with a maximal testing accuracy of 64.1% and a maximal cross-validation consistency of 10 out of 10 (P = 0.0156). Allelic distribution of the 518 Thr/Thr polymorphism in MMEL1 primarily suggests its independent and synergistic contribution towards CD susceptibility among Saudi patients. Lack of significant association of IRAK and SH2B3 gene polymorphisms in Saudi patients but their association in European groups suggests the genetic heterogeneity of CD.
authors: Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Omar I
authors: OI
authors: Saadah
authors: Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Noor Ahmad
authors: NA
authors: Shaik
authors: Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Babajan
authors: B
authors: Banaganapalli
authors: Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Mohammed A
authors: MA
authors: Salama
authors: Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Sameer E
authors: SE
authors: Al-Harthi
authors: Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; BGI, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors: Jun
authors: J
authors: Wang
authors: Department of Pediatrics, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia.
authors: Harbi A
authors: HA
authors: Shawoosh
authors: Department of Pediatrics, Division of Gastroenterology, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia.
authors: Sharifa A
authors: SA
authors: Alghamdi
authors: Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
authors: Yagoub Y
authors: YY
authors: Bin-Taleb
authors: Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
authors: Bakr H
authors: BH
authors: Alhussaini
authors: Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Ramu
authors: R
authors: Elango
authors: Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Jumana Y
authors: JY
authors: Al-Aama
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002446:Celiac Disease / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D015260:Neprilysin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D012529:Saudi Arabia
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C490778:SH2B3 protein, human; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; C436550:MMEL1 protein, human; D015260:Neprilysin