INT103910

Context Info Confidence 0.47 First Reported 2002 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 19 Total Number 19 Disease Relevance 12.24 Pain Relevance 2.93

cytosol (NOD2) plasma membrane (NOD2) enzyme binding (NOD2) cytoplasm (NOD2)

Anatomy Link Frequency corpus 2 proximal region 1 NOD2 (Homo sapiens)

Pain Link Frequency Relevance Heat Crohn's disease 269 100.00 spinal inflammation 10 100.00 Inflammation 171 98.24 rheumatoid arthritis 2 96.36 abdominal pain 6 90.36 cytokine 26 86.24 Inflammatory response 10 58.60 Pain 6 51.20 Inflammatory stimuli 1 49.08 psoriasis 5 9.84

Disease Link Frequency Relevance Heat Disease 523 100.00 Low Back Pain 10 100.00 Hyperplasia 25 99.84 Mycobacterial Infection 6 99.24 Nicotine Addiction 103 99.00 Biliary Liver Cirrhosis 75 98.28 INFLAMMATION 161 98.24 Disease Susceptibility 17 98.24 Crohn's Disease 4 97.60 Sarcoidosis 5 96.48

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

No study has yet examined the possible association of NOD2/CARD15 mutations with patients with LNH.

NOD2 Binding (association) of associated with hyperplasia

1) Confidence 0.47 Published 2006 Journal J. Pediatr. Gastroenterol. Nutr. Section Abstract Doc Link 16819374 Disease Relevance 0.80 Pain Relevance 0.14

No study has yet examined the possible association of NOD2/CARD15 mutations with patients with LNH.

CARD15 Binding (association) of associated with hyperplasia

2) Confidence 0.47 Published 2006 Journal J. Pediatr. Gastroenterol. Nutr. Section Abstract Doc Link 16819374 Disease Relevance 0.80 Pain Relevance 0.14

Associations between NOD2 polymorphisms and several clinical features of AS, including disease severity assessed by questionnaire and age at spondylarthritis onset, were also investigated.

NOD2 Binding (Associations) of

3) Confidence 0.46 Published 2002 Journal Arthritis Rheum. Section Body Doc Link 12115195 Disease Relevance 0.08 Pain Relevance 0

Lack of association of ankylosing spondylitis with the most common NOD2 susceptibility alleles to Crohn's disease.

NOD2 Binding (association) of associated with spinal inflammation, crohn's disease and disease

4) Confidence 0.37 Published 2003 Journal J. Rheumatol. Section Title Doc Link 12508397 Disease Relevance 0.20 Pain Relevance 0.29

OBJECTIVE: To investigate whether the 3 most common mutations in the NOD2 gene that confer susceptibility to Crohn's disease (CD) are also associated with ankylosing spondylitis (AS).

NOD2 gene Binding (associated) of associated with spinal inflammation, crohn's disease and disease

5) Confidence 0.37 Published 2003 Journal J. Rheumatol. Section Abstract Doc Link 12508397 Disease Relevance 0.35 Pain Relevance 0.26

For example, using the pattern with $GENE$/$GENE$, the system will extract the co-occurrence pairs (CARD15, NOD2) and (MMAC, PTEN) from the following sentence fragments found in the corpus respectively:

CARD15 Binding (extract) of in corpus

6) Confidence 0.36 Published 2005 Journal BMC Bioinformatics Section Body Doc Link PMC1090552 Disease Relevance 0.09 Pain Relevance 0

For example, using the pattern with $GENE$/$GENE$, the system will extract the co-occurrence pairs (CARD15, NOD2) and (MMAC, PTEN) from the following sentence fragments found in the corpus respectively:

NOD2 Binding (extract) of in corpus

7) Confidence 0.36 Published 2005 Journal BMC Bioinformatics Section Body Doc Link PMC1090552 Disease Relevance 0.09 Pain Relevance 0

Ileal lymphonodular hyperplasia is not associated with NOD2/CARD15 mutations.

CARD15 Binding (associated) of associated with hyperplasia

8) Confidence 0.36 Published 2006 Journal J. Pediatr. Gastroenterol. Nutr. Section Title Doc Link 16819374 Disease Relevance 0.82 Pain Relevance 0.13

Ileal lymphonodular hyperplasia is not associated with NOD2/CARD15 mutations.

NOD2 Binding (associated) of associated with hyperplasia

9) Confidence 0.36 Published 2006 Journal J. Pediatr. Gastroenterol. Nutr. Section Title Doc Link 16819374 Disease Relevance 0.81 Pain Relevance 0.13

The present study confirms a strong association of NOD2/CARD15 gene variants, and to a lesser extent the coding ATG16L1 variant and the OCTN1/OCTN2 haplotype, with CD in a relatively small Polish Caucasian patient group.

CARD15 Binding (association) of associated with crohn's disease

10) Confidence 0.36 Published 2008 Journal BMC Med Genet Section Body Doc Link PMC2535589 Disease Relevance 1.11 Pain Relevance 0.17

NOD2/CARD15 mutations are also associated with susceptibility to other granulomatous inflammatory disorders, such as early-onset sarcoidosis and Blau syndrome [21,22].

CARD15 Binding (associated) of associated with inflammation, syndrome and sarcoidosis

11) Confidence 0.35 Published 2008 Journal BMC Med Genet Section Body Doc Link PMC2535589 Disease Relevance 0.53 Pain Relevance 0.17

The present study confirms a strong association of NOD2/CARD15 gene variants, and to a lesser extent the coding ATG16L1 variant and the OCTN1/OCTN2 haplotype, with CD in a relatively small Polish Caucasian patient group.

NOD2 Binding (association) of associated with crohn's disease

12) Confidence 0.34 Published 2008 Journal BMC Med Genet Section Body Doc Link PMC2535589 Disease Relevance 1.11 Pain Relevance 0.17

NOD2/CARD15 mutations are also associated with susceptibility to other granulomatous inflammatory disorders, such as early-onset sarcoidosis and Blau syndrome [21,22].

NOD2 Binding (associated) of associated with inflammation, syndrome and sarcoidosis

13) Confidence 0.32 Published 2008 Journal BMC Med Genet Section Body Doc Link PMC2535589 Disease Relevance 0.53 Pain Relevance 0.17

The Caspase Recruitment Activation Domain 15 (NOD2/CARD15) gene is located in the proximal region of chromosome 16 (16q12) and encodes the nucleotide-binding oligomerization domain protein 2 (NOD2), which is a cytosolic receptor for a bacterial peptidoglycan response pathway [19].

NOD2 Binding (binding) of in proximal region

14) Confidence 0.32 Published 2008 Journal BMC Med Genet Section Body Doc Link PMC2535589 Disease Relevance 0.36 Pain Relevance 0.11

One hypothesis is that with the loss of binding of muramyl dipeptide to NOD2, there is a compensatory response with failure to inhibit the activation of c-Rel and p50 by binding of peptidoglycan to the toll-like receptor 2.58 This results in the downstream activation of IL-12 and consequent inflammation.

NOD2 Binding (binding) of associated with inflammation

15) Confidence 0.22 Published 2007 Journal J Gastroenterol Section Body Doc Link PMC2780674 Disease Relevance 0.64 Pain Relevance 0.09

Nod2 recognizes muramyl dipeptide of peptidoglycan from intracellular pathogens and activates NF-?

Nod2 Binding (recognizes) of

16) Confidence 0.18 Published 2010 Journal BMC Genomics Section Body Doc Link PMC2996966 Disease Relevance 0.24 Pain Relevance 0

CARD-15 variants in CD are associated with modifications in nuclear factor-?

CARD-15 Binding (associated) of associated with disease

17) Confidence 0.16 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2621411 Disease Relevance 0.94 Pain Relevance 0.14

It is stimulated by Mycobacterium tuberculosis [22] and it synergizes with NOD1 and NOD2 ligands to stimulate IL-1?

NOD2 Binding (ligands) of associated with mycobacterial infection

18) Confidence 0.09 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2288676 Disease Relevance 0.94 Pain Relevance 0.38

CARD15, IBD5 and IL23R) well known to be associated with CD did not show up in this study as these genes are not predominant in the group of CD patients, and because this genome-wide gene association study focused on the smoking phenotype.

CARD15 Binding (associated) of associated with nicotine addiction and crohn's disease

19) Confidence 0.07 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2708910 Disease Relevance 1.82 Pain Relevance 0.44

General Comments

This test has worked.