Published ahead of print on March 4, 2005, doi:10.1164/rccm.200405-658OC Am. J. Respir. Crit. Care Med., Volume 171, Number 10, May 2005, 1136-1141 A more recent version of this article appeared on May 15, 2005
Submitted on May 20, 2004 Study of C-C Chemokine Receptor 2 Alleles in Sarcoidosis, With Emphasis on Family Based AnalysisRuta Valentonyte1,1 Department of General Internal Medicine and Kiel Center of the German National Genotyping Platform, Christian-Albrechts-University, University Clinics Schleswig-Holstein Campus, Kiel, Germany, 2 Institute for Medical Informatics and Statistics, Christian-Albrechts-University, University Clinics Schleswig-Holstein Campus, Kiel, Germany, 3 Department of Pneumology, University of Freiburg, Freiburg, Germany, 4 Institute of Human Genetics, University of Lubeck, Lubeck, Germany * To whom correspondence should be addressed. E-mail: schuerma{at}medinf.mu-luebeck.de.
Prevailing models of sarcoidosis pathogenesis involve the activation of alveolar macrophages, aggregation of CD4+ T lymphocytes, and their accumulation in epithelioid cell granulomas. Increasing evidence suggests that each of these steps is modified by the host genetic constitution. Consequently, candidate susceptibility genes have been selected based on their potential function under this model. The C-C chemokine receptor 2 (CCR2) is involved in Th1 immune activity by recruiting competent cells and possibly by balancing response. CCR2 gene variants have shown to be associated with sarcoidosis or - more specifically - with Lofgren's syndrome, a distinct form of acute sarcoidosis. We have studied three CCR2 gene polymorphisms (c.190G>A, c.840C>T and c.4385A>T) in an extended sample of 1203 sarcoidosis patients and their relatives. Case-control comparisons and family-based genetic analyses did not support previous findings of an association between CCR2 gene variability and the risk of sarcoidosis. However, they confirmed linkage disequilibrium and showed positive linkage results (p = 0.034) and therefore suggest a susceptibility gene in the surrounding chromosomal region. Key words: Genotype, Transmission Disequilibrium Test, Genetic Predisposition to Disease, Lofgren's syndrome
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