Am. J. Respir. Cell Mol. Biol., Volume 22, Number 6, June, 2000 672-675

The Natural Resistance-Associated Macrophage Protein Gene in African Americans with Sarcoidosis

Mary J. Maliarik, Kang Mei Chen, Roberta G. Sheffer, Benjamin A. Rybicki, Marcie L. Major, John Popovich Jr., and Michael C. Iannuzzi

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, and Department of Biostatistics and Research Epidemiology, Henry Ford Health Sciences Center, Detroit, Michigan

The histologic and clinical similarities between tuberculosis and sarcoidosis suggest a shared underlying pathophysiology. Human natural resistance-associated macrophage protein (NRAMP1), which is closely related to the mouse gene, has been associated with susceptibility to tuberculosis in some human populations. Given the importance of the Nramp1 gene in animal models of granulomatous disorders, the association with human tuberculosis, and the possible role of NRAMP1 in macrophage activation and function, we hypothesized that human NRAMP1 plays a role in susceptibility to sarcoidosis. We analyzed several NRAMP1 gene polymorphisms in a case-control study of 157 African American patients with sarcoidosis and 111 African American control subjects. Our results, in contrast to those in tuberculosis patients, showed that the less common genotypes were found more often in control subjects than in case patients (odds ratio, 0.48; 95% confidence interval, 0.28-0.81). In particular, one polymorphism, a (CA)_n repeat in the immediate 5' region of the gene, was found to have a protective effect (P = 0.014). Whereas NRAMP1 polymorphisms have been associated with increased susceptibility to tuberculosis, our results suggest that at least one NRAMP1 polymorphism may decrease susceptibility in sarcoidosis.

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