PMID- 10898108
OWN - NLM
STAT- MEDLINE
DCOM- 20001109
LR  - 20191025
IS  - 0960-314X (Print)
IS  - 0960-314X (Linking)
VI  - 10
IP  - 5
DP  - 2000 Jul
TI  - Characterization of two highly polymorphic human tryptase loci and comparison 
      with a newly discovered monkey tryptase ortholog.
PG  - 389-96
AB  - 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.
FAU - Guida, M
AU  - Guida M
AD  - PPGx Incorporated, La Jolla, CA 92037, USA. marco.guida@ppgx.com
FAU - Riedy, M
AU  - Riedy M
FAU - Lee, D
AU  - Lee D
FAU - Hall, J
AU  - Hall J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Pharmacogenetics
JT  - Pharmacogenetics
JID - 9211735
RN  - 0 (Genetic Markers)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.- (chymase 2)
RN  - EC 3.4.21.39 (Chymases)
RN  - EC 3.4.21.59 (Tryptases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Chymases
MH  - Genetic Markers
MH  - Humans
MH  - Macaca fascicularis
MH  - Mast Cells/*enzymology
MH  - Molecular Sequence Data
MH  - *Polymorphism, Genetic
MH  - Polymorphism, Single Nucleotide
MH  - Sequence Homology, Amino Acid
MH  - Sequence Homology, Nucleic Acid
MH  - Serine Endopeptidases/*genetics
MH  - Tryptases
EDAT- 2000/07/18 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/07/18 11:00
PHST- 2000/07/18 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/07/18 11:00 [entrez]
AID - 10.1097/00008571-200007000-00002 [doi]
PST - ppublish
SO  - Pharmacogenetics. 2000 Jul;10(5):389-96. doi: 10.1097/00008571-200007000-00002.