PMID- 12684584
OWN - NLM
STAT- MEDLINE
DCOM- 20030610
LR  - 20080513
IS  - 1533-001X (Print)
IS  - 1533-001X (Linking)
VI  - 3 Suppl 1
DP  - 2003
TI  - Clinical applications of advances in the genetics of IBD.
PG  - S9-17
AB  - Our rapidly expanding understanding of the genetics of inflammatory bowel disease 
      (IBD) has led to important clinical applications. It is becoming apparent that 
      genes help determine the clinical phenotype, intestinal and extraintestinal 
      complications, response to treatment, and drug toxicities in these disorders. For 
      example, NOD2/CARD15 mutations are associated with ileal Crohn's disease, 
      possibly with a fibrosing/obstructing phenotype, but do not influence responses 
      to infliximab treatment. Similarly, certain human leukocyte antigen (HLA) 
      haplotypes are associated with aggressive, extensive ulcerative colitis and 
      strongly influence extraintestinal manifestations of IBD, including uveitis and 
      various forms of arthritis. Expression of the glucocorticoid receptor b 
      determines the clinical response to corticosteroids, whereas genetically 
      regulated levels of enzymes metabolizing 6-mercaptopurine/azathioprine may 
      determine clinical responses and toxicities to these important immunosuppressive 
      agents. Once we have a more sophisticated understanding of the mechanisms of 
      genetic defects in IBD, it may be feasible to restore physiologic function to 
      prevent the onset of disease in susceptible individuals. However, because we do 
      not have the ability to prevent disease at the present time, it is premature to 
      screen offspring and first-degree relatives of IBD patients for the NOD2/CARD15 
      genotype. One can anticipate that it will become feasible to prospectively 
      determine a patient's genotype and to individualize a drug regimen, leading to 
      highly effective, safe treatments for IBD patients on a rational, rather than 
      empiric, basis.
FAU - Sartor, R Balfour
AU  - Sartor RB
AD  - Departments of Medicine, Microbiology, and Immunology/Division of Digestive 
      Diseases, University of North Carolina, Chapel Hill, NC, USA.
LA  - eng
GR  - DK40249/DK/NIDDK NIH HHS/United States
GR  - DK53347/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Rev Gastroenterol Disord
JT  - Reviews in gastroenterological disorders
JID - 101140143
RN  - 0 (Carrier Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NOD2 protein, human)
RN  - 0 (Nod2 Signaling Adaptor Protein)
SB  - IM
MH  - Carrier Proteins/genetics
MH  - Colitis, Ulcerative/epidemiology/*genetics/immunology
MH  - Crohn Disease/epidemiology/*genetics/immunology
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Immune Tolerance
MH  - *Intracellular Signaling Peptides and Proteins
MH  - Nod2 Signaling Adaptor Protein
MH  - Signal Transduction
EDAT- 2003/04/10 05:00
MHDA- 2003/06/11 05:00
CRDT- 2003/04/10 05:00
PHST- 2003/04/10 05:00 [pubmed]
PHST- 2003/06/11 05:00 [medline]
PHST- 2003/04/10 05:00 [entrez]
PST - ppublish
SO  - Rev Gastroenterol Disord. 2003;3 Suppl 1:S9-17.