NRAMP1 genetic polymorphisms as a risk factor of tuberculous pleurisy.
METHODS
Nrampl encoded by the NRAMP1 gene influences the phagolysosomal function of alveolar macrophage against Mycobacterium tuberculosis. Genetic polymorphisms of NRAMP1 affect innate host resistance through the defective production and function of Nrampl.


OBJECTIVE
To investigate this relationship, the NRAMP1 polymorphisms in patients with tuberculous pleurisy were determined.


METHODS
Pleural biopsy proven 56 patients were designated to the pleurisy group and 45 healthy adults were designated to the healthy control group. Three NRAMP1 polymorphisms such as single nucleotide change in intron 4(469 + 14G/C, INT4), a non-conservative single-base substitution at codon 543(D543N) and TGTG deletion in the 3' untranslated region (1729 + 55del4, 3'UTR) were determined.


RESULTS
The frequencies of mutant genotypes of INT4 and 3'UTR were significantly high in the pleurisy group (P = 0.01, P = 0.02), but the frequencies of D543N were not significantly different between the two groups. Odds ratios (OR), which are a comparison of the wild with the mutant genotype, were 8.02 (95%CI 2.42 approximately 26.57) for INT4 and 5.73 (95%CI 1.14 approximately 28.92) for 3'UTR which were statistically significant. In the combined analysis of the INT4 and 3'UTR, the ORs were 6.00 (95%CI 1.46 approximately 24.64) for GC/++ genotype and 14.00 (95%CI 1.61 approximately 121.75) for GC/+del when compared with GG/++; these differences were statistically significant.


CONCLUSIONS
The NRAMP1 genetic polymorphisms, especially INT4 and 3'UTR, were closely related to tuberculous pleurisy.
Pulmonary Division, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
J H
JH
Kim
S Y
SY
Lee
S H
SH
Lee
C
C
Sin
J J
JJ
Shim
K H
KH
In
S H
SH
Yoo
K H
KH
Kang
D000328:Adult; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007723:Korea / Q000453:epidemiology; D008297:Male; D008969:Molecular Sequence Data; D016017:Odds Ratio; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011336:Probability; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014396:Tuberculosis, Pleural / Q000453:epidemiology / Q000235:genetics*; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1