title: Susceptibility to ulcerative colitis in Hungarian patients determined by gene-gene interactions.
abstract: OBJECTIVE
  To study the inflammatory bowel disease-5 locus (IBD5) and interleukin-23 receptor (IL23R) gene variants in UC patients and test for gene-gene interaction.
  
  
  METHODS
  The study population (n = 625) was comprised of 320 unrelated ulcerative colitis (UC) patients with Caucasian origin and 316 age- and gender-matched, healthy controls. Five variants in the IBD5 locus (IGR2198a_1 rs11739135, IGR2096a_1 rs12521868, IGR2230a_1 rs17622208, SLC22A4 rs1050152 and SLC22A5 rs2631367) and two of the IL23R gene (rs1004819, rs2201841) were analysed. PCR and restriction fragment length polymorphism methods were used for genotyping, the SLC22A4 rs1050152 genotypes were determined by direct sequencing. Interactions and specific genotype combinations of the seven variants were tested by binary logistic regression analysis. The IL23R genotypes were stratified by IBD5 genotypes for further interaction analyses.
  
  
  RESULTS
  For the IL23R rs1004819 A allele we found significantly higher allele frequency (P = 0.032) in UC patients compared to control subjects. The SNP rs1004819 showed significant association with UC risk for carriers (P = 0.004, OR = 1.606; 95%CI: 1.160-2.223) and the SNP rs2201841 for homozygotes (P = 0.030, OR = 1.983; 95%CI: 1.069-3.678). Individually none of the IBD5 markers conferred risk to UC development. There was no evidence for statistical interaction either between IBD5 loci and IL23R genes using logistic regression analysis. After genotype stratification, we could detect a positive association on the background of rs1004819 A allele for SLC22A4 T, SLC22A5 C, IGR2198a_1 C or IGR2096a_1 T allele, the highest OR was calculated in the presence of SLC22A4 T allele (P = 0.005, OR = 2.015; 95%CI: 1.230-3.300). There was no association with UC for any combinations of rs1004819 and IGR2230a_1. The IL23R rs2201841 homozygous genotype and IBD5 carrier status together did not confer susceptibility for UC.
  
  
  CONCLUSIONS
  The present study has shown that UC susceptibility genes are likely to act in a complex interactive manner similar to CD.
authors.affiliation: Patricia Sarlos, 1 Department of Internal Medicine, University of Pecs, 7623 Pecs, Hungary.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sarlos
authors.affiliation: Patricia Sarlos, 1 Department of Internal Medicine, University of Pecs, 7623 Pecs, Hungary.
authors.forename: Dalma
authors.initials: D
authors.lastname: Varszegi
authors.affiliation: Patricia Sarlos, 1 Department of Internal Medicine, University of Pecs, 7623 Pecs, Hungary.
authors.forename: Veronika
authors.initials: V
authors.lastname: Csongei
authors.affiliation: Patricia Sarlos, 1 Department of Internal Medicine, University of Pecs, 7623 Pecs, Hungary.
authors.forename: Lili
authors.initials: L
authors.lastname: Magyari
authors.affiliation: Patricia Sarlos, 1 Department of Internal Medicine, University of Pecs, 7623 Pecs, Hungary.
authors.forename: Luca
authors.initials: L
authors.lastname: Jaromi
authors.affiliation: Patricia Sarlos, 1 Department of Internal Medicine, University of Pecs, 7623 Pecs, Hungary.
authors.forename: Lajos
authors.initials: L
authors.lastname: Nagy
authors.affiliation: Patricia Sarlos, 1 Department of Internal Medicine, University of Pecs, 7623 Pecs, Hungary.
authors.forename: Bela
authors.initials: B
authors.lastname: Melegh
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D027701:Organic Cation Transport Proteins / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics; D012307:Risk Factors; D027981:Symporters; D044465:White People / Q000235:genetics
chemical_list: C515500:IL23R protein, human; D027701:Organic Cation Transport Proteins; D018123:Receptors, Interleukin; C109807:SLC22A4 protein, human; D027981:Symporters
keywords: Gene-gene interaction; Inflammatory bowel disease; Inflammatory bowel disease-5 locus; Interleukin-23 receptor gene; Ulcerative colitis