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* From the Division of Pulmonary and Critical Care Medicine, Departments of Medicine (Drs. Koh, Kwon, and E.J. Kim), Radiology (Dr. Lee), and Laboratory Medicine (Drs. Ki, and J.W. Kim), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Correspondence to: O. Jung Kwon, MD, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, Gangnam-gu, Seoul 135–710, South Korea; e-mail: ojkwon{at}smc.samsung.co.kr
Study objectives: Pulmonary disease caused by nontuberculous mycobacteria (NTM) may occur in patients with no underlying lung disease and no known immunodeficiency. The purpose of this study was to evaluate a potential role for natural-resistance-associated macrophage protein 1 (NRAMP1) gene polymorphisms for human susceptibility to the NTM lung disease.
Design: A case-control study.
Setting: Tertiary university medical center.
Participants: Forty-one adult patients with NTM lung disease (Mycobacterium avium complex infection, 18 patients; Mycobacterium abscessus infection, 23 patients) were included in the study population. The diagnosis of NTM lung disease was made when the patients fulfilled the diagnostic criteria published by the American Thoracic Society. All patients had findings on high-resolution CT scans, such as bilateral bronchiectasis combined with multiple small nodules and branching linear structures, that were characteristic of the nodular bronchiectatic form of NTM lung disease. Fifty healthy individuals were selected as control subjects.
Results: Heterozygotes at intron 4 (469 + 14G/C) [INT4], codon 543 in exon 15 (D543N), and 3' untranslated region (3'UTR) were observed at significantly higher frequencies in patients with NTM lung disease than in control subjects. The odds ratios (ORs) were 2.78 (95% confidence interval [CI], 1.12 to 6.89; p = 0.026) for INT4 G/C, 5.74 (95% CI, 1.48 to 22.30; p = 0.006) for D543 G/A, and 9.54 (95% CI, 2.49 to 36.53; p < 0.001) for 3'UTR TGTG+/del. Subjects who were heterozygous for two NRAMP1 polymorphisms in INT4 and D543N were particularly overrepresented among those with NTM lung disease, compared with those with the most common NRAMP1 genotype (OR, 10.88, 95% CI, 1.18 to 100.45; p = 0.035). There were no significant differences in the frequencies of INT4, D543N, and 3'UTR polymorphisms between the patients with M avium complex infection and those with M abscessus infection.
Conclusions: These findings suggest that the NRAMP1 genetic polymorphisms are associated with human susceptibility to NTM lung disease.
Key Words: atypical mycobacteria • cation transport proteins • genetic predisposition to disease • lung diseases • polymorphism
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