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Published online before print April 25, 2007
Eur Respir J 2007, doi:10.1183/09031936.00042506
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ORIGINAL ARTICLE

Pulmonary Mycobacterium avium complex infection: Association with NRAMP1 polymorphisms

G. Tanaka 1, J. Shojima 1, I. Matsushita 1, H. Nagai 2, A. Kurashima 3, K. Nakata 1, E. Toyota 4, N. Kobayashi 4, K. Kudo 4, N. Keicho 1*

1 Dept of Respiratory Diseases, Research Institute, International Medical Center of Japan, Tokyo, Japan
2 Division of Respiratory Disease, National Hospital Organization Tokyo Hospital, Tokyo, Japan
3 Division of Clinical Research, National Hospital Organization Tokyo Hospital, Tokyo, Japan
4 Division of Respiratory Disease, International Medical Center of Japan, Tokyo, Japan


  Abstract

We aimed to elucidate risk factors for non-immunocompromized pulmonary Mycobacterium avium complex (MAC) infection.

We analyzed epidemiological data and variations of candidate genes for mycobacterial diseases in 111 patients with pulmonary MAC infection. Four polymorphisms of the human natural resistance-associated macrophage protein (NRAMP1) gene, 5'(GT)n, 469+14 G/C, D543N and 3'UTR (TGTG) insertion/deletion were genotyped by the PCR-based methods. Fok I and Taq I polymorphisms of the vitamin D receptor gene and -221 X/Y and codon 54 A/B polymorphisms of the mannose binding lectin gene were also evaluated.

Females were more susceptible to MAC and the right middle lobe or lingular segment of the lung was mainly affected. Patients' residence at the onset of the disease was distributed evenly irrespective of waterfronts or city water supply system. As compared with homozygotes for major alleles of D543N and TGTG insertion/deletion polymorphism of the NRAMP1 gene, heterozygotes containing minor alleles were less often observed in MAC cases than in controls. This genetic effect was further significant in the patients without comorbidity (p<0.01), but not in the patients with comorbidity. Other polymorphisms did not show any association with the MAC infection.

The NRAMP1 gene might be involved in susceptibility to pulmonary MAC infection.

Keywords:  Mannose binding lectin, Mycobacterium avium complex, natural resistance-associated macrophage protein 1, vitamin D receptor




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[Abstract] [Full Text] [PDF]


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