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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2000-10-27
pubmed:abstractText
Tryptases are serine proteases involved in mast cell-mediated inflammatory responses which represent potential targets of drugs against diseases such as asthma, arthritis and inflammatory bowel disease. In order to interpret pharmacodynamic data on the tryptase inhibitors undergoing clinical trials, we defined the genetic variability of the tryptase 1 (TPS1) and tryptase 2 (TPS2) loci by screening a reference population of 32 individuals representing three major ethnic groups (Caucasian, African American, Asian). Using overlapping PCR products, we resequenced the entire tryptase genes with the only exclusion of TPS2 intron 1 and 20 bp of TPS2 5' untranslated region included in exon 1 and we identified 21 novel single nucleotide polymorphisms in TPS1 and 17 single nucleotide polymorphisms plus a large polymorphic deletion in the TPS2 gene. We also compared the type, frequency and distribution of single nucleotide polymorphisms in TPS1 and TPS2 and we observed that the polymorphism frequency within these two loci is unexpectedly high (approximately 1 SNP every 90 bp) and that some of the allele frequencies differ significantly among the three ethnic groups. Based on differences observed in preclinical studies using a cynomolgus monkey (Macaca fascicularis) asthma model system, we investigated the difference between monkey and human tryptase genes in order to better understand the mechanism of action of our tryptase inhibitors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0960-314X
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
389-96
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Characterization of two highly polymorphic human tryptase loci and comparison with a newly discovered monkey tryptase ortholog.
pubmed:affiliation
PPGx Incorporated, La Jolla, CA 92037, USA. marco.guida@ppgx.com
pubmed:publicationType
Journal Article, Comparative Study