PMID- 25386052
OWN - NLM
STAT- MEDLINE
DCOM- 20150810
LR  - 20181113
IS  - 2219-2840 (Electronic)
IS  - 1007-9327 (Print)
IS  - 1007-9327 (Linking)
VI  - 20
IP  - 41
DP  - 2014 Nov 7
TI  - Immunogenetic biomarkers in inflammatory bowel diseases: role of the IBD3 region.
PG  - 15037-48
LID - 10.3748/wjg.v20.i41.15037 [doi]
AB  - Many studies have demonstrated the linkage between the IBD3 region (6p21.1-23), 
      an area which encompasses the famous human leukocyte antigen (HLA) complex, and 
      Crohn's disease (CD) or ulcerative colitis (UC). IBD3 is the only region that 
      meets genome-wide significance, and provides stronger evidence of the linkage 
      than 16p13.1-16q12.2 (IBD1), the locus that contains the susceptibility gene 
      CARD15. However, despite these findings, IBD3 susceptibility genes remain elusive 
      and unclear due to the strong linkage disequilibrium, extensive polymorphism, and 
      high gene density that characterize this area and also due to varying allele 
      frequencies in populations around the world. This area presents an extremely high 
      abundance of genes, including the classical and non-classical major 
      histocompatibility complex (MHC) class I and II genes, and other genes, namely 
      MHC class III genes tumor necrosis factor (TNF)-alpha and -beta, and Hsp, whose proteins 
      play key functions in immunological processes. To date, it is not clear which 
      genes within the MHC family contribute to the IBD pathogenesis, although certain 
      HLA alleles have been associated with IBD. Recent insights into the biological 
      function of other genes encoded within the IBD3 region, such as the MHC class I 
      chain-related (MIC) genes, have led investigators to a more comprehensive 
      exploration of this region. MHC class I chain-related molecule A (MICA) is highly 
      polymorphic and interacts with NKG2D, its receptor on the surface of NK, Tgammadelta and 
      T CD8(+) cells. Increased expression of MICA in intestinal epithelial cells and 
      increased expression of NKG2D in CD4(+) T cells (lamina propria) in patients with 
      CD have also been reported. MICA alleles have also been associated with IBD, and 
      a variation at amino acid position 129 of the alpha2-heavy chain domain seems to 
      categorize MICA alleles into strong and weak binders of NKG2D receptor, thereby 
      influencing the effector cells' function. In this regard, a relevant role of 
      MICA-129-Val/Met single nucleotide polymorphism has recently been implicated in 
      the pathogenesis of IBD. TNF-alpha and -beta also play an important role in inflammatory 
      response. In fact, IBD is commonly treated with TNF-alpha inhibitors. Additionally, 
      polymorphisms of TNF-alpha gene are known to affect the gene expression level and 
      particular TNF-alpha genotypes may influence the response of IBD patients treated 
      with TNF-alpha inhibitors.
FAU - Muro, Manuel
AU  - Muro M
AD  - Manuel Muro, Ruth Lopez-Hernandez, Anna Mrowiec, Centro de Investigacion 
      Biomedica en Red de Enfermedades Hepaticas y Digestivas (Ciberehd), Immunology 
      Service, University Hospital Virgen de la Arrixaca, 30120 Murcia, Spain.
FAU - Lopez-Hernandez, Ruth
AU  - Lopez-Hernandez R
AD  - Manuel Muro, Ruth Lopez-Hernandez, Anna Mrowiec, Centro de Investigacion 
      Biomedica en Red de Enfermedades Hepaticas y Digestivas (Ciberehd), Immunology 
      Service, University Hospital Virgen de la Arrixaca, 30120 Murcia, Spain.
FAU - Mrowiec, Anna
AU  - Mrowiec A
AD  - Manuel Muro, Ruth Lopez-Hernandez, Anna Mrowiec, Centro de Investigacion 
      Biomedica en Red de Enfermedades Hepaticas y Digestivas (Ciberehd), Immunology 
      Service, University Hospital Virgen de la Arrixaca, 30120 Murcia, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - World J Gastroenterol
JT  - World journal of gastroenterology
JID - 100883448
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Biological Products)
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Lymphotoxin-alpha)
RN  - 0 (MHC class I-related chain A)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/therapeutic use
MH  - Biological Products/therapeutic use
MH  - Colitis, Ulcerative/diagnosis/drug therapy/*genetics/immunology
MH  - Crohn Disease/diagnosis/drug therapy/*genetics/immunology
MH  - Genetic Predisposition to Disease
MH  - HLA Antigens/*genetics/immunology
MH  - Histocompatibility Antigens Class I/*genetics/immunology
MH  - Humans
MH  - Lymphotoxin-alpha/*genetics
MH  - Molecular Targeted Therapy
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide
MH  - Risk Factors
MH  - Treatment Outcome
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/*genetics/immunology
PMC - PMC4223237
OTO - NOTNLM
OT  - HLA
OT  - IBD3
OT  - Inflammatory bowel disease
OT  - MICA
OT  - Tumor necrosis factor
EDAT- 2014/11/12 06:00
MHDA- 2015/08/11 06:00
PMCR- 2014/11/07
CRDT- 2014/11/12 06:00
PHST- 2013/09/20 00:00 [received]
PHST- 2014/03/01 00:00 [revised]
PHST- 2014/04/15 00:00 [accepted]
PHST- 2014/11/12 06:00 [entrez]
PHST- 2014/11/12 06:00 [pubmed]
PHST- 2015/08/11 06:00 [medline]
PHST- 2014/11/07 00:00 [pmc-release]
AID - 10.3748/wjg.v20.i41.15037 [doi]
PST - ppublish
SO  - World J Gastroenterol. 2014 Nov 7;20(41):15037-48. doi: 
      10.3748/wjg.v20.i41.15037.