title: Two independent genetic factors responsible for the associations of the IBD5 locus with Crohn's disease in the Czech population.
abstract: BACKGROUND
  The role of the IBD5 locus in development of Crohn's disease (CD) has not been clarified. In the Czech population we examined its genetic association using variants of the SLC22A4 (rs1050152), SLC22A5 (rs2631367), two single nucleotide polymorphisms (SNPs) shown to be associated with CD in genome-wide studies (rs6596075 and rs2188962), and four SNPs previously shown to tag the haplotype blocks 4, 7, 9, 10 of the IBD5 locus (IGR2063b_1, IGR2230a_1, IGR100Xa_1, IGR3236a_1).
  
  
  METHODS
  The genotype, phenotype, and allelic frequencies were compared between 469 unrelated patients with CD (177 pediatric-onset, 292 adult-onset) and 470 unrelated healthy controls, all Caucasians of Czech ancestry.
  
  
  RESULTS
  The most significant difference between patients and controls was found for the SNP rs6596075 (odds ratio [OR] = 0.70 for the G allele; 95% CI 0.52-0.94) in the dominant model and SNP IGR2063b_1 (OR = 1.38 for the G allele; 95% CI 1.14-1.67) in the log-additive model. We found a strong linkage disequilibrium across the IBD5 locus except rs6596075. The haplotype consisting of minor alleles of all tested SNPs except rs6596075 was carried by 31% patients and 23% control subjects (OR = 1.35, 95% CI 1.06-1.72). The association of variants in SLC22A4 and SLC22A5 was dependent on this risk haplotype, while the strong association of the rs6596075 was seemingly independent. In the analysis of subphenotypes we found only an association of the penetrating disease with rs6596075 (OR = 2.13; 95% CI 1.31-3.47).
  
  
  CONCLUSIONS
  Our study confirms the importance of IBD5 in determining CD susceptibility, and demonstrates that two independent genetic factors may be responsible for the association observed within this locus.
authors.affiliation: Department of Pediatrics, University Hospital Motol and Second Faculty of Medicine, Charles University in Prague, Czech Republic. ondrej.hradsky@lfmotol.cuni.cz
authors.forename: Ondrej
authors.initials: O
authors.lastname: Hradsky
authors.forename: Petra
authors.initials: P
authors.lastname: Dusatkova
authors.forename: Martin
authors.initials: M
authors.lastname: Lenicek
authors.forename: Jiri
authors.initials: J
authors.lastname: Bronsky
authors.forename: Dana
authors.initials: D
authors.lastname: Duricova
authors.forename: Jiri
authors.initials: J
authors.lastname: Nevoral
authors.forename: Libor
authors.initials: L
authors.lastname: Vitek
authors.forename: Milan
authors.initials: M
authors.lastname: Lukas
authors.forename: Ondrej
authors.initials: O
authors.lastname: Cinek
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D018153:Czech Republic / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; D055815:Young Adult
chemical_list: D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters