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Pulmonary Mycobacterium avium complex infection: association with NRAMP1 polymorphisms

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

CORRESPONDENCE: N. Keicho, Dept of Respiratory Diseases, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. Fax: 81 332071038. E-mail: keicho{at}ri.imcj.go.jp

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

Received: March 25, 2006
Accepted April 18, 2007

The present study aimed to elucidate risk factors for nonimmunocompromised pulmonary Mycobacterium avium complex (MAC) infection.

Epidemiological data and variations of candidate genes for mycobacterial diseases were analysed in 111 patients with pulmonary MAC infection. Four polymorphisms of the human natural resistance-associated macrophage protein (NRAMP)1 gene, the 5'(GT)n, 469+14 G/C, D543N and the 3'untranslated region (3'TGTG) insertion/deletion, were genotyped using 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 infection mainly affecting the right middle lobe or lingular segment of the lung. Patients' residence at the onset of the disease was distributed evenly irrespective of a waterfront or city water supply system. As compared with homozygotes for major alleles of the 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 more significant in patients without comorbidity but not in patients with comorbidity. Other polymorphisms did not show any association with the MAC infection.

The human natural resistance-associated macrophage protein 1 gene might be involved in susceptibility to pulmonary Mycobacterium avium complex infection.

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