PMID- 16953235
OWN - NLM
STAT- MEDLINE
DCOM- 20070720
LR  - 20161124
IS  - 1470-269X (Print)
IS  - 1470-269X (Linking)
VI  - 7
IP  - 3
DP  - 2007 Jun
TI  - Analysis of a missense variant of the human N-formyl peptide receptor that is 
      associated with agonist-independent beta-arrestin association and indices of 
      inflammation.
PG  - 190-9
AB  - Formyl-Met-Leu-Phe (fMLP) is a potent chemoattractant molecule released from both 
      bacteria and damaged mitochondria that activates fMLP receptors (FPR) leading to 
      neutrophil chemotaxis, degranulation and superoxide production. A common missense 
      single nucleotide polymorphism in the human FPR1 gene at nucleotide c.32C>T 
      results in the amino-acid substitution, p.I11T, in the FPR1 extracellular 
      amino-terminus. The minor (c.32T) allele frequencies were 0.25, 0.27, 0.25, 0.15 
      and 0.14 in healthy Caucasian, African, East Indian, Chinese and Native Canadian 
      individuals, respectively. In subjects homozygous for the p.T11 allele, we find 
      elevated serum concentrations of C-reactive protein, increased absolute counts of 
      blood leukocytes and neutrophils, and erythrocyte sedimentation rates. When 
      expressed in HEK 293 and RBL-2H3 cells a substantial proportion of FPR1 p.I11T 
      variant is retained intracellularly and agonist-independent internalization of 
      the FPR1 p.I11T variant, but not the wild-type FPR1, is constitutively associated 
      with beta-arrestin2-GFP in vesicles. Moreover, basal N-acetyl-D-glucosaminidase 
      release is increased in primary neutrophils isolated from subjects either 
      heterozygous or homozygous for the FPR1 p.T11 allele. Taken together, the data 
      suggest an increased receptor activity and phenotypic expression of increased 
      inflammatory indices in subjects with the p.T11 allele.
FAU - Bhattacharya, M
AU  - Bhattacharya M
AD  - Cell Biology Research Group, The University of Western Ontario, London, ON, 
      Canada.
FAU - Wang, J
AU  - Wang J
FAU - Ribeiro, F M
AU  - Ribeiro FM
FAU - Dixon, S J
AU  - Dixon SJ
FAU - Feldman, R D
AU  - Feldman RD
FAU - Hegele, R A
AU  - Hegele RA
FAU - Ferguson, S S G
AU  - Ferguson SS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060905
PL  - United States
TA  - Pharmacogenomics J
JT  - The pharmacogenomics journal
JID - 101083949
RN  - 0 (Arrestins)
RN  - 0 (FPR1 protein, human)
RN  - 0 (Receptors, Formyl Peptide)
RN  - 0 (beta-Arrestins)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Arrestins/*physiology
MH  - C-Reactive Protein/*analysis
MH  - Cell Degranulation
MH  - Cell Line
MH  - Cytoskeleton/metabolism
MH  - Humans
MH  - Inflammation/*etiology
MH  - *Mutation, Missense
MH  - Neutrophils/physiology
MH  - Polymorphism, Single Nucleotide
MH  - Receptors, Formyl Peptide/*genetics
MH  - beta-Arrestins
EDAT- 2006/09/06 09:00
MHDA- 2007/07/21 09:00
CRDT- 2006/09/06 09:00
PHST- 2006/09/06 09:00 [pubmed]
PHST- 2007/07/21 09:00 [medline]
PHST- 2006/09/06 09:00 [entrez]
AID - 6500416 [pii]
AID - 10.1038/sj.tpj.6500416 [doi]
PST - ppublish
SO  - Pharmacogenomics J. 2007 Jun;7(3):190-9. doi: 10.1038/sj.tpj.6500416. Epub 2006 
      Sep 5.