Brief Article
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World J Gastroenterol. Jan 7, 2014; 20(1): 219-227
Published online Jan 7, 2014. doi: 10.3748/wjg.v20.i1.219
Susceptibility to ulcerative colitis in Hungarian patients determined by gene-gene interactions
Patricia Sarlos, Dalma Varszegi, Veronika Csongei, Lili Magyari, Luca Jaromi, Lajos Nagy, Bela Melegh
Patricia Sarlos, 1st Department of Internal Medicine, University of Pecs, 7623 Pecs, Hungary
Dalma Varszegi, Department of Dermatology, Venereology and Oncodermatology, University of Pecs, 7624 Pecs, Hungary
Veronika Csongei, Department of Immunology and Biotechnology, University of Pecs, 7624 Pecs, Hungary
Lili Magyari, Luca Jaromi, Bela Melegh, Department of Medical Genetics, University of Pecs, 7624 Pecs, Hungary
Veronika Csongei, Lili Magyari, Luca Jaromi, Bela Melegh, Szentagothai Research Centre, 7624 Pecs, Hungary
Lajos Nagy, Institute of Family Medicine, University of Pecs, 7632 Pecs, Hungary
Author contributions: Sarlos P, Varszegi D, Csongei V, Magyari L, Jaromi L, Nagy L and Melegh B contributed equally to this work; Sarlos P, and Nagy L wrote the manuscript; Sarlos P, Csongei V, and Jaromi L performed the statistical analyses; Varszegi D, Magyari L and Melegh B carried out the experiments.
Supported by The Grant of the Hungarian Science Foundation Nos. OTKA K103983 and T73430
Correspondence to: Bela Melegh, MD, PhD, DSc, Department of Medical Genetics, University of Pecs, Szigeti 12, 7624 Pecs, Hungary. bela.melegh@aok.pte.hu
Telephone: +36-72-536427 Fax: +36-72-536427
Received: August 28, 2013
Revised: September 29, 2013
Accepted: December 13, 2013
Published online: January 7, 2014
Processing time: 144 Days and 18.9 Hours
Abstract

AIM: 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.

CONCLUSION: The present study has shown that UC susceptibility genes are likely to act in a complex interactive manner similar to CD.

Keywords: Gene-gene interaction; Interleukin-23 receptor gene; Inflammatory bowel disease-5 locus; Ulcerative colitis; Inflammatory bowel disease

Core tip: Most of the identified inflammatory bowel disease genes individually have only modest effects on inflammatory bowel disease susceptibility, suggesting that complex interactions are more important. The authors investigated the gene-gene interactions of the inflammatory bowel disease-5 loci and IL23R susceptibility alleles in a Hungarian ulcerative colitis cohort. The exploration of high risk genotype combinations could further add to our knowledge about the development of ulcerative colitis and could facilitate the diagnosis of high-risk patients.