Functional analysis of SNPs associated with ulcerative colitis in the NKX2. 3 gene.

• Project/Area Number: 22890019
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: SHIGA Hisashi 東北大学, 病院, 医員 (20583355)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,068,000 (Direct Cost: ¥2,360,000、Indirect Cost: ¥708,000); Fiscal Year 2011: ¥1,469,000 (Direct Cost: ¥1,130,000、Indirect Cost: ¥339,000); Fiscal Year 2010: ¥1,599,000 (Direct Cost: ¥1,230,000、Indirect Cost: ¥369,000)
• Keywords: 潰瘍性大腸炎 / クローン病 / 感受性遺伝子 / NKX2. 3 / NKX2.3 / allelic imbalance

Research Abstract

NKX2. 3 is a promising candidate for susceptibility genes to inflammatory bowel disease (IBD). The aim of this study was to perform a candidate gene analysis of NKX2. 3 in Japanese IBD and to examine how the risk allele (haplotype)affects susceptibility to IBD using allelic expression ratios of NKX2. 3 mRNA in the involved colonic mucosa. Two SNPs (rs10883365 and rs888208)were significantly associated with UC and 1 SNP (rs10883365)was associated with CD. Haplotype B formed by the 3 SNPs demonstrated a significant association with UC. Subgroup analyses indicated that rs10883365 was significantly associated mainly with colonic CD. The allelic expression ratios of NKX2. 3 mRNA transcribed from haplotype B (risk haplotype)to haplotype A (non-risk haplotype)in the involved mucosa from 10 IBD patients were significantly higher than the allelic ratio of respective genomic DNA. We confirmed the association of SNP rs10883365 located in the 5' flanking region of NKX2-3 with Japanese UC and colonic CD and determined the risk haplotype (haplotype B)for UC. The demonstrated allelic expression imbalance supports the idea that the risk haplotype of NKX2. 3 confers susceptibility to UC through increasing expression of NKX2. 3 mRNA in the colonic mucosa.

Research Products

• [Journal Article] 炎症性腸疾患の遺伝的要因・疾患感受性遺伝子 (2012)
  • Author(s): 木内喜孝、高橋成一、遠藤克哉、志賀永嗣、下瀬川徹
  • Journal Title: 日本臨床 Volume: 70 Pages: 66-71
• [Journal Article] 症性腸疾患の遺伝的要因・疾患感受性遺伝子 (2012)
  • Author(s): 木内喜孝、志賀永嗣, 他
  • Journal Title: 日本臨床 Volume: 70 Pages: 66-71
• [Journal Article] IBDの遺伝子異常-GWASがもたらした病態研究の糸口- (2011)
  • Author(s): 木内喜孝、荒井壮、金澤義丈、角田洋一、遠藤克哉、志賀永嗣、高橋成一、下瀬川徹
  • Journal Title: Intestine Volume: 15 Pages: 415-421
• [Journal Article] Increased expression of NKX2. 3 mRNA transcribed from the risk haplotype for ulcerative colitis in the involved colonic mucosa (2011)
  • Author(s): Arai T, Kakuta Y, Kinouchi Y, Kimura T, Negoro K, Aihara H, Endo K, Shiga H, Kanazawa Y, Kuroha M, Moroi R, Nagasawa H, Shimodaira Y, Takahashi S, Shimosegawa T
  • Journal Title: Hum Immunol Volume: 72(7) Pages: 587-91
  • Peer Reviewed
• [Journal Article] Increased expression of NKX2.3 mRNA transcribed from the risk haplotype for ulcerative colitis in the involved colonic mucosa (2011)
  • Author(s): Arai T, Shiga H, et al
  • Journal Title: Hum Immunol Volume: 72 Pages: 587-591
  • Peer Reviewed