Candidate gene analysis of the IL12B gene in Crohn's disease

• Project/Area Number: 22790628
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: ENDO Katsuya 東北大学, 高等教育開発推進センター, 助教 (40509197)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: クローン病 / 感受性遺伝子 / IL12b / allelic imbalance / IL12B / allelic expression imbalance

Research Abstract

IL12B is one of the promising candidates for susceptibility genes to Crohn's disease (CD). The aim of this study was to do a candidate gene analysis of IL12B in Japanese CD, and to determine how the risk allele affects the susceptibility to CD. Therefore, allelic expression imbalance of IL-12B mRNA was determined in peripheral monocytes. A total of 364 patients with CD, 242 patients with ulcerative colitis (UC) and445 healthy controls (HCs) were examined. Eight SNPs around IL12B were genotyped. The allelic ratio of IL12B-mRNA was examined using SNaPshot analysis in LPS-stimulated monocytes. Two SNPs (rs6887695, rs41292470) were significantly associated with CD (Pc = 0.012, 0.020, respectively) and one SNP (rs3212227) showed an association with marginal significance (Pc = 0.10). Haplotype A formed by these three SNPs showed significant association with CD (Pc = 0.00054, odds ratio = 1.46). The allelic ratios of IL12B-mRNA transcribed from the haplotype A to the non-risk haplotype (haplotype B) in LPS-stimulated monocytes from ten healthy controls heterozygous for the risk haplotype were significantly higher than the allelic ratio of respective genomic DNA (p= 0.00069). We confirmed the association of the haplotype 1 of IL12B with Japanese CD. The demonstrated allelic expression imbalance supports the idea that the risk haplotype of IL12B confers susceptibility to CD through increasing expression of IL12B-mRNA.

Research Products

• [Presentation] The IL12B gene is associated with the clinical course of Crohn's disease in Japanese patients (2010)
  • Author(s): Kakuta Y, Kinouchi Y, Shimodaira Y, Moroi R, Nagasawa H, Kuroha M, Arai T, Kanazawa Y, Shiga H, Endo K, Takahashi S, Shimosegawa T
  • Organizer: 18th United European Gastroenterology Week
  • Place of Presentation: スペインBarcelona