Analysis of IL12B Gene Variants in German Patients With Inflammatory Bowel Disease

Abstract

Introduction: IL12B encodes the p40 subunit of IL-12, which is also part of IL-23. Recent genome-wide association studies identified IL12B and IL23R as susceptibility genes for inflammatory bowel disease (IBD). However, in contrast to the confirmed association with IL23R, there are discrepant results regarding the association of IL12B with IBD in different populations. Methods: We therefore analyzed IL12B gene variants regarding association with Crohn's disease (CD) and ulcerative colitis (UC) in the German population. Genomic DNA from 2196 individuals of Caucasian origin including 913 CD patients, 318 UC patients and 965 healthy, unrelated controls was analyzed for four SNPs in the IL12B gene (rs3212227, rs17860508, rs10045431, rs6887695). From all study participants, blood samples were taken and genomic DNA was isolated from peripheral blood leukocytes using the DNA blood mini kit from Qiagen (Hilden, Germany) according to the manufacturer's guidelines. Genotyping was performed by PCR and melting curve analysis using a pair of fluorescence resonance energy transfer (FRET) probes in a LightCycler480 Instrument (Roche Diagnostics, Mannheim, Germany). Results: Our analysis revealed no association of the four analyzed IL12B SNPs with susceptibility to CD and UC. The detailed results are shown in Table 1. However, there was a trend for rs6887695 for association with CD (OR 1.41; [95% CI 0.99- 1.31]) and UC (1.18 [95% CI 0.97-1.43]), which did not achieve statistical signficance. Conclusions: In contrast to IL23R gene variants, IL12B variants do not play a major role in the susceptibility to CD and UC in the German population. Given the trend for a weak association of IL12B rs6887695 with CD and UC, a disease-modifying effect can not be completely excluded. However, the strength of a potential association of IL12B with IBD would be several log-fold weaker than that shown for IL23R in our cohort, suggesting a more important role for IL-23R than IL-12/23 p40 in the genetic susceptibility to IBD. Association of IL12B gene markers in CD and UC case-control association studies. Minor allele frequencies (MAF), allelic test p-values, and. (Table presented).