Published ahead of print on May 28, 2003, doi:10.1164/rccm.200302-221OC
Am. J. Respir. Crit. Care Med., Volume 168, Number 3, August 2003, 330-334
A more recent version of this article appeared on August 1, 2003
Submitted on February 18, 2003
Accepted on May 14, 2003
COMPLEMENT RECEPTOR 1 GENE POLYMORPHISMS ARE ASSOCIATED WITH IDIOPATHIC PULMONARY FIBROSIS
Michele Zorzetto1, Ilaria Ferrarotti1, Rocco Trisolini2, Luigi Lazzari Agli2, Roberta Scabini1, Monique Novo3, Annalisa De Silvestri4, Marco Patelli2, Miryam Martinetti5, MariaClara Cuccia6, Venerino Poletti7, Ernesto Pozzi3, and Maurizio Luisetti3*
1 Laboratorio di Biochimica e Genetica, Clinica di Malattie dell'Apparato Respiratorio, IRCCS Policlinico San Matteo, Pavia, Italy; Dipartimento di Genetica e Microbiologia, Universita degli Studi, Pavia, Italy,
2 Unita Operativa di Endoscopia Toracica, Dipartimento di Scienze Oncologiche, Ospedale Maggiore, Bologna, Italy,
3 Laboratorio di Biochimica e Genetica, Clinica di Malattie dell'Apparato Respiratorio, IRCCS Policlinico San Matteo, Pavia, Italy,
4 Servizio di Patologia Neonatale, IRCCS Policlinico San Matteo, Pavia, Italy,
5 Servizio di Immunoematologia e Trasfusione, Centro di Immunologia dei Trapianti, IRCCS Policlinico San Matteo, Pavia, Italy,
6 Dipartimento di Genetica e Microbiologia, Universita degli Studi, Pavia, Italy,
7 Dipartimento di Malattie dell'Apparato Respiratorio e del Torace, Ospedale GB Morgagni, Forli, Italy
* To whom correspondence should be addressed. E-mail: m.luisetti{at}smatteo.pv.it.
Idiopathic pulmonary fibrosis is a chronic, fibrotic disorder underlaid by aberrant wound healing of repeated lung injury. Environmental triggers and genetic background are likely to act as modifiers of the fibrotic response. Erythrocyte complement receptor 1 is a membrane protein mediating the transport of immune complexes to phagocytes. Three gene polymorphisms are related to erythrocyte surface density of complement receptor 1 molecules, in turn related to the rate of immune complexe clearance. There is evidence of association between sarcoidosis and the complement receptor 1 gene. We wondered whether idiopathic pulmonary fibrosis is associated with the complement receptor 1 gene alleles coding for a reduced molecule/erythrocyte ratio. We studied 74 patients and 166 controls. Three polymorphic sites of the gene, A3650G exon 22, HindIII RFLP intron 27, and C5507G exon 33, were analyzed, and found to be in linkage disequilibrium. The GG genotype for the C5507G exon 33 polymorphism was significantly more common in patients with idiopathic pulmonary fibrosis than in controls (odds ratio = 6.232, 95% confidence interval = 2.198-18.419, P = 0.00023). The significant difference was found in both genders. These findings agree with speculations on the role of the complement receptor 1 gene in idiopathic pulmonary fibrosis.
Key words: Polymerase Chain Reaction, Gene Sequencing, Candidate Gene, Association Study, Immune Complexes.
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