Correlation Between Primary Tuberculous Pleurisy and NRAMP1 Genetic Polymorphism

Kim, Je Hyeong; Kim, Byung Gyu; Jung, Ki Hwan; Lee, Sang Youb; Park, Sang Myun; Lee, Sin Hyung; Sin, Cheol; Cho, Jae Youn; Shim, Jae Jeong; In, Kwang Ho; Yoo, Se Hwa; Kang, Kyung Ho

Abstract

BACKGROUND: The phagolysosomal function of alveolar macrophage against M. tuberculosis infection is influenced by Nramp1, which is encoded by the NRAMP1 gene. There are several genetic polymorphisms in NRAMP1, and these polymorphisms affect the innate host resistance through the defect in production and function of Nramp1. To investigate this relationship, we determined the NRAMP1 genetic polymorphism in patients with primary tuberculous pleurisy was determined.
METHODS
: 56 Fifty-six primary tuberculous pleurisy patient (,) who were diagnosed by pleural biopsy(,) were designated to the pleurisy group and 45 healthy adults were designated to the healthy control group. 3 Three genetic polymorphisms of NRAMP1 (,) such as a single point mutation in intron 4(469+14G/C, INT4), a nonconservative single-base substitution at codon 543 that changes aspartic acid to asparagine(D543N) and a TGTG deletion in the 3' untranslated region(1729+55del4, 3'UTR)(,) were determined. Polymerase chain reaction(PCR) and polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) were used.
RESULTS
The frequencies of mutanat mutant genotypes of INT4 and 3'UTR were significantly high in pleurisy group(p=0.001, p=0.023). But the frequencies of D543N were not significantly different between the both two groups(p=0.079). Odds The odds ratios(,) which are a comparison with wild genotype for determining mutant genotypes(,) were 8.022(95% confidence interval=2.422 ~26.572) for INT4 and 5.733(95% confidence interval=1.137 ~28.916) for 3'UTR which were ;these were statistically significant. But the odds ratio for D543N was not significant. In the combined analysis of the INT4 and 3'UTR polymorphisms, as compared with GG/++ homozygotes, (delete) the odds ratios were 6.000(95% confidence interval=1.461 ~ 24.640) for GC/++ genotype and 14.000(95% confidence interval=1.610 ~121.754) for GC/+del when compared with GG/++ homozygotes which ;these were statisticallysignificant.
CONCLUSION
Among the NRAMP1 genetic polymorphisms, a single point mutation in intron 4(469+14G/C, INT4) and a TGTG deletion in the 3' untranslated region(1729+55del4, 3'UTR) were closely related to the primary tuberculous pleurisy.