Association of NRAMP 1 Gene Polymorphism with Susceptibility to Tuberculosis in Taiwanese Aboriginals
Article Outline
Background/Purpose
The human homologue of mice natural-resistance-associated macrophage protein 1 (Nramp 1) gene, NRAMP 1, has been reported to play a role in susceptibility to tuberculosis in humans. The aboriginal population in Taiwan has a five-fold higher prevalence of tuberculosis than people of Han ethnicity. Whether genetic factors such as NRAMP 1 polymorphism play a role in the prevalence of tuberculosis in Taiwanese aboriginals should be clarified.
Methods
NRAMP 1 polymorphism was studied using a case-control design of patients with tuberculosis, including subjects of Han (Hans) and aboriginal ethnicity in Hualien, eastern Taiwan. The polymorphisms of NRAMP 1 at loci INT4, D543N, 77-385C/T, 3-UTR (CAAA) deletion and 5-(CA)n microsatellite markers were assessed by polymerase chain reaction on tissue DNA isolated from 105 aborigines and 110 Hans with tuberculosis. Comparable numbers of ethnically-matched controls were studied simultaneously.
Results
Two NRAMP 1 polymorphisms, INT4 and 5-(CA)n, were significantly associated with susceptibility to tuberculosis in aboriginals (p = 0.0070 and p = 0.0031, respectively). However, no association was detected at the five loci of NRAMP 1 polymorphisms among Hans (p > 0.08).
Conclusion
Genetic variation in NRAMP 1 may affect susceptibility to and increase risk for tuberculosis in Taiwanese aboriginals. Although environmental factors play an important role in tuberculosis infection, genetic factors such as NRAMP 1 polymorphism may also contribute to the high prevalence of tuberculosis in Taiwanese aboriginals.
Key Words: Hans , NRAMP 1 gene , polymorphism , Taiwanese aboriginals , tuberculosis
No full text is available. To read the body of this article, please view the PDF online.
References
- NRAMP1 polymorphisms, susceptibility and clinical features of tuberculosis . J Infect . 2003;46:215–220
- . Susceptibility to mycobacterial infections: the importance of host genetics . Genes Immun . 2003;4:4–11
- Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans . N Engl J Med. . 1998;338:640–644
- Linkage of tuberculosis to chromosome 2q35 loci, including NRAMP1, in a large aboriginal Canadian family . Am J Hum Genet . 2000;67:405–416
- Identification of polymorphisms and sequence variants in the human homologue of the mouse natural resistance-associated macrophage protein gene . Am J Hum Genet . 1995;56:845–853
- The Ity/Lsh/Bcg locus: natural resistance to infection with intracellular parasites is abrogated by disruption of the Nramp1 gene . J Exp Med. . 1995;182:655–666
- Variants of the human NRAMP1 gene and susceptibility to tuberculosis in Morocco . Int J Tuberc Lung Dis . 2003;7:599–602
- . The natural resistance-associated macrophage protein and susceptibility to intracellular pathogens . Microbes Infect . 1999;1:23–27
- . The Bcg host-resistance gene . Clin Infect Dis . 2000;31(Suppl 3):S81–S85
- Natural resistance-associated macrophage protein 1 polymorphisms are associated with microscopy-positive tuberculosis . J Infect Dis . 2002;186:517–521
- Variations in the NRAMP1 gene and susceptibility of tuberculosis in Taiwanese . Int J Tuberc Lung Dis . 2002;6:454–460
- Promoter polymorphism of SLC11A1 (formerly NRAMP1) confers susceptibility to autoimmune type 1 diabetes mellitus in Japanese . Tissue Antigens . 2004;63:231–236
- . In: 2004 Annual Report: Highlights of Activities in 2003 and Future Prospects . Taipei: Center for Disease Control, Taiwan; 2004;p. 47–51
- Complex segregation and linkage analysis of familial gout in Taiwanese aborigines . Arthritis Rheum . 2004;50:242–246
- Differentiation of BCG-induced lymphadenitis from tuberculosis in lymph node biopsy specimens by molecular analyses of pncA and oxyR . J Pathol . 1998;184:96–102
- The linkage disequilibrium maps of three human chromosomes across four populations reflect their demographic history and a common underlying recombination pattern . Genome Res. . 2005;15:454–462
- Assessment of two flexible and compatible SNP genotyping platforms: TaqMan SNP Genotyping Assays and the SNPlex Genotyping System . Mutat Res. . 2005;573:111–135
- Identification of C to T mutation at position −236 bp in the human NRAMP1 gene promoter . Immunogenetics . 1996;44:309–311
- Identification of a highly polymorphic length variant in the 3'UTR of NRAMP1 . Immunogenetics . 1995;42:428–429
- Variants of the natural resistance-associated macrophage protein 1 gene (NRAMP1) are associated with severe forms of pulmonary tuberculosis . Clin Infect Dis . 2005;40:1232–1236
- NRAMP1 genetic polymorphisms as a risk factor of tuberculous pleurisy . Int J Tuberc Lung Dis . 2003;7:370–375
- 3'UTR polymorphisms in the NRAMP1 gene are associated with susceptibility to tuberculosis in Koreans . Int J Tuberc Lung Dis . 2000;4:577–580
- The origin of Minnan and Hakka, the so-called “Taiwanese”, inferred by HLA study . Tissue Antigens . 2001;57:192–199
- SLC11A1 (formerly NRAMP1) and disease resistance . Cell Microbiol . 2001;3:773–784
- Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg . Cell . 1993;73:469–485
- The Bcg/Ity/Lsh locus: genetic transfer of resistance to infections in C57BL/6J mice transgenic for the Nramp1 Gly169 allele . Infect Immun . 1996;64:2923–2929
PII: S0929-6646(09)60131-5
doi:10.1016/S0929-6646(09)60131-5
© 2006 Formosan Medical Association & Elsevier. Published by Elsevier Inc. All rights reserved.
