| Budget Amount *help |
¥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)
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| 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.
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