INT67374

Context Info Confidence 0.74 First Reported 1996 Last Reported 2009 Negated 2 Speculated 1 Reported most in Body Documents 15 Total Number 37 Disease Relevance 49.10 Pain Relevance 8.07

cytoskeleton (Mefv) nucleus (Mefv) intracellular (Mefv) cytoplasm (Mefv)

Anatomy Link Frequency joints 1 monocytes 1 abdomen 1 chest 1 neutrophils 1 Mefv (Mus musculus)

Pain Link Frequency Relevance Heat Crohn's disease 1886 99.68 Pain 9 98.92 abdominal pain 34 98.76 Inflammation 474 97.32 Arthritis 26 85.52 Angina 4 85.20 cva 2 64.24 imagery 3 58.16 spastic colon 3 25.00 rheumatoid arthritis 23 5.00

Disease Link Frequency Relevance Heat Fever 449 100.00 Familial Mediterranean Fever 56 100.00 Syndrome 42 100.00 Colitis 184 99.92 Inflammatory Bowel Disease 2740 99.80 Disease 2229 99.68 Abdominal Pain 34 98.76 Pain 3 98.68 Common Cold 1 96.88 INFLAMMATION 403 96.76

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Pyrin is mainly expressed in neutrophils and monocytes and is among the proteins involved in the interleukin-1 inflammatory pathway.

Gene_expression (expressed) of Pyrin in monocytes associated with inflammation

1) Confidence 0.74 Published 2003 Journal Eur. J. Pediatr. Section Abstract Doc Link 12751000 Disease Relevance 2.02 Pain Relevance 0.30

Also, given that common variants in the NLRP3 region have previously been associated with CD [3] and that the gene products of NLRP3 and MEFV (i.e.

Gene_expression (products) of MEFV associated with crohn's disease

2) Confidence 0.68 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745755 Disease Relevance 1.19 Pain Relevance 0.49

Based on the identification of six common SNPs in the NLRP3 region contributing to CD susceptibility [3] and reports that the NLRP3 and MEFV gene products interact with each other and are involved in similar pathways, we sought to evaluate whether possible gene-gene interaction between the MEFV tagging SNPs and the NLRP3 six common SNPs could have masked an MEFV contribution to CD susceptibility.

Gene_expression (products) of MEFV associated with crohn's disease

3) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745755 Disease Relevance 0.98 Pain Relevance 0.26

Several mutations have been identified of which the homozygous form of the M694V mutation is associated with a more severe expression of FMF.

Gene_expression (expression) of FMF associated with fever

4) Confidence 0.62 Published 2003 Journal Eur. J. Obstet. Gynecol. Reprod. Biol. Section Abstract Doc Link 12781406 Disease Relevance 1.73 Pain Relevance 0.17

This clinical and epidemiological evidence linking IBD to the MEFV gene, together with the co-localization of the MEFV and NLRP3 gene products (pyrin and NALP3, respectively) within the same signaling pathway, suggested that MEFV could also contribute to CD and/or UC susceptibility.

Gene_expression (products) of pyrin associated with inflammatory bowel disease and crohn's disease

5) Confidence 0.60 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745755 Disease Relevance 1.82 Pain Relevance 0.16

Mefv expression is significantly increased in trinitrobenzene sulfonic acid (TNBS)-induced (fold change ?

Gene_expression (expression) of Mefv

6) Confidence 0.60 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745755 Disease Relevance 1.59 Pain Relevance 0.15

The up-regulation of MEFV gene expression in the CD and UC patients, as well as in the mouse models, can be explained by the broad involvement of pyrin, the MEFV encoded protein, in the regulation of the inflammasome molecular platform and the inflammatory process [12]–[18].

Gene_expression (expression) of MEFV associated with inflammatory bowel disease, inflammation and crohn's disease

7) Confidence 0.60 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745755 Disease Relevance 1.92 Pain Relevance 0.56

Although these mutations are found throughout the gene, five sequence alterations in MEFV represent the majority of FMF chromosomes, four of which are clustered in exon 10 (i.e.

Gene_expression (chromosomes) of FMF associated with fever

8) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745755 Disease Relevance 1.50 Pain Relevance 0.25

Sequencing and subsequent genotyping of variants located in this associated haplotype block identified three synonymous variants (D102D/rs224225, G138G/rs224224, A165A/rs224223) and one non-synonymous variant (R202Q/rs224222) located in MEFV exon 2 that were significantly associated with UC (rs224222: p?

Gene_expression (exon) of MEFV associated with inflammatory bowel disease

9) Confidence 0.59 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2745755 Disease Relevance 1.66 Pain Relevance 0.30

No epistatic interactions are observed between NLRP3 and MEFV in the CD and UC combined Belgian-Canadian sample set

Neg (No) Gene_expression (observed) of MEFV associated with inflammatory bowel disease and crohn's disease

10) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745755 Disease Relevance 1.03 Pain Relevance 0.23

Only coding SNPs within MEFV exon 2 (i.e. rs224225, rs224224, rs224223, and rs224222) were significantly associated with UC in the Belgian samples.

Gene_expression (exon) of MEFV associated with inflammatory bowel disease

11) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745755 Disease Relevance 0.91 Pain Relevance 0.20

block region of MEFV and UC in the exploratory phase, we excluded possible coding risk variants and non-MEFV genes located in this 5?

Gene_expression (region) of MEFV associated with inflammatory bowel disease

12) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745755 Disease Relevance 1.03 Pain Relevance 0.30

To assess this latter possibility, since we knew that the MEFV and the NLRP3 gene product interacted with each other, we genotyped the six SNPs in the NLRP3 region that had been previously associated with CD [3] in both the Belgian and Canadian UC sample sets and performed gene-gene interaction analysis using these six NLRP3 SNPs and the 16 SNPs genotyped in the MEFV region (i.e. 12 tagging SNPs and 4 coding SNPs in MEFV exon 2 region).

Gene_expression (product) of MEFV associated with inflammatory bowel disease and crohn's disease

13) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745755 Disease Relevance 0.26 Pain Relevance 0.05

MEFV mutations in exon 10 do not contribute to CD and UC susceptibility

Gene_expression (mutations) of MEFV associated with inflammatory bowel disease and crohn's disease

14) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745755 Disease Relevance 1.65 Pain Relevance 0.27

Although these mutations are found throughout the gene, five sequence alterations in MEFV represent the majority of FMF chromosomes, four of which are clustered in exon 10 (i.e.

Gene_expression (alterations) of MEFV associated with fever

15) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745755 Disease Relevance 1.50 Pain Relevance 0.25

block region of MEFV and UC in the exploratory phase, we excluded possible coding risk variants and non-MEFV genes located in this 5?

Gene_expression (located) of non-MEFV associated with inflammatory bowel disease

16) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745755 Disease Relevance 1.02 Pain Relevance 0.28

However, significant associations were observed with three synonymous variants located in MEFV exon 2 (D102D/rs224225(C), G138G/rs224224(G), A165A/rs224223(A)) and UC in the Belgian combined sample set (p?

Gene_expression (exon) of MEFV associated with inflammatory bowel disease

17) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745755 Disease Relevance 0.52 Pain Relevance 0.10

In the third UC case-control cohort from Scotland (Edinburgh) (Table 1), only the A allele of tagging SNP rs224215 located in MEFV intron 2 was significantly associated with UC (p?

Gene_expression (intron) of MEFV associated with inflammatory bowel disease

18) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745755 Disease Relevance 0.91 Pain Relevance 0.12

UTR region of MEFV, as well as the region encompassing the promoter to intron 4 of ZNF200 (Figure 2).

Gene_expression (region) of MEFV

19) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2745755 Disease Relevance 0.49 Pain Relevance 0.09

No specific diagnostic tests are commercially available for FMF so identifying the characteristic clinical picture of FMF is important.

Neg (No) Gene_expression (available) of FMF associated with fever

20) Confidence 0.59 Published 2009 Journal Hokkaido Igaku Zasshi Section Abstract Doc Link 19998717 Disease Relevance 0.95 Pain Relevance 0.16

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