title: CARD15/NOD2, CD14 and toll-like 4 receptor gene polymorphisms in Saudi patients with Crohn's Disease.
abstract: Crohn's disease (CD) is a multifactorial disease with a genetic component and an observed association with genes related to the innate immune response. Polymorphisms in the CARD15/NOD2 gene, in addition to functional variants of the toll-like receptor-4 (TLR4) and CD14 genes, have been associated with the development of Crohn's disease. There is no information about the frequency of these polymorphisms in the Saudi population. We examined the frequency of the three major CARD15/NOD2 risk alleles (Leu1007fsinsC, Arg702Trp, and Gly908Arg) and the TLR4 (Thr399Il) polymorphism as well as a functional polymorphism in the promoter of the CD14-159C/T in 46 Saudi CD patients and 50 matched controls. Genotyping was performed by allele-specific PCR or by restriction fragment length polymorphism (PCR-RFLP) analysis. The mutant genotype frequencies of the Leu1007fsinsC, Arg702Trp and Gly908Arg in the patient group were 6.5, 21.7 and 6.5%, respectively, compared with frequencies of 0, 4 and 2%, respectively, in the control group. There were 15 patients who carried the mutant alleles for all three CARD15/NOD2 variants, Leu1007fsinsC, Arg702Trp and Gly908Arg, while none of the control candidates carried the three alleles. This genetic study provides evidence that the three major CARD15/NOD2 variant alleles and the CD14 -159C/T polymorphism are associated with Crohn's disease (CD) susceptibility in the Saudi population; however, there is no evidence that the TLR4 (Thr399Il) or CARD15/NOD2 polymorphisms can be considered risk factors for Crohn's disease.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University King Saud, Riyadh 11461, Saudi Arabia.
authors.forename: Nahla
authors.initials: N
authors.lastname: Azzam
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Alexandria, Alexandria 21111, Egypt.
authors.forename: Howaida
authors.initials: H
authors.lastname: Nounou
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University King Saud, Riyadh 11461, Saudi Arabia.
authors.forename: Othman
authors.initials: O
authors.lastname: Alharbi
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University King Saud, Riyadh 11461, Saudi Arabia.
authors.forename: Abedulrahman
authors.initials: A
authors.lastname: Aljebreen
authors.affiliation: Department of Biochemistry, Faculty of Science, King Saud University, Riyadh 11495, Saudi Arabia.
authors.forename: Manal
authors.initials: M
authors.lastname: Shalaby
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012529:Saudi Arabia; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D055815:Young Adult
chemical_list: D018950:Lipopolysaccharide Receptors; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D051197:Toll-Like Receptor 4