Related Experiment Videos
Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans
R Bellamy1, C Ruwende, T Corrah
1Wellcome Trust Centre for Human Genetics, Oxford University, United Kingdom.
Background:
Genetic factors may affect the susceptibility to tuberculosis, but no specific genes governing susceptibility have been identified. In mice, natural resistance to infection with some mycobacteria is influenced by the gene for natural-resistance-associated macrophage protein 1 (Nramp1), but the role of the human homologue of this gene, NRAMP1, in tuberculosis is unknown. We typed polymorphisms in NRAMP1 in a case-control study of tuberculosis in the Gambia, West Africa.
Methods:
Sequence-specific oligonucleotide hybridization and microsatellite analysis were used to type NRAMP1 polymorphisms in 410 adults (mean age, 34.7 years) with smear-positive pulmonary tuberculosis and 417 ethnically matched, healthy controls. Patients with human immunodeficiency virus infection were excluded.
Results:
Four NRAMP1 polymorphisms were each significantly associated with tuberculosis. Subjects who were heterozygous for two NRAMP1 polymorphisms in intron 4 and the 3' untranslated region of the gene were particularly overrepresented among those with tuberculosis, as compared with those with the most common NRAMP1 genotype (odds ratio, 4.07; 95 percent confidence interval, 1.86 to 9.12; chi-square= 14.58; P<0.001).
Conclusions:
Genetic variation in NRAMP1 affects susceptibility to tuberculosis in West Africans.
Insights
Genetic variations in the NRAMP1 gene are linked to tuberculosis susceptibility in West Africa. Specific NRAMP1 polymorphisms significantly increase the risk of developing tuberculosis in this population.
Area of Science:
- Genetics
- Infectious Diseases
- Immunology
Background:
- Tuberculosis susceptibility is influenced by genetic factors, though specific genes remain unidentified.
- The mouse Nramp1 gene impacts mycobacterial resistance, but the human NRAMP1 gene's role in tuberculosis is unclear.
- This study investigates NRAMP1 polymorphisms in a West African population.
Purpose of the Study:
- To investigate the association between NRAMP1 gene polymorphisms and tuberculosis susceptibility.
- To identify specific NRAMP1 variants that may confer risk or protection against tuberculosis.
Main Methods:
- A case-control study was conducted in The Gambia, West Africa.
- NRAMP1 polymorphisms were analyzed in 410 tuberculosis patients and 417 healthy controls using oligonucleotide hybridization and microsatellite analysis.
- Individuals with HIV infection were excluded from the study.
Main Results:
- Four NRAMP1 polymorphisms showed a significant association with tuberculosis.
- Heterozygosity for two NRAMP1 polymorphisms (intron 4 and 3' UTR) was strongly linked to increased tuberculosis risk (OR=4.07, P<0.001).
Conclusions:
- Genetic variation within the NRAMP1 gene plays a role in determining tuberculosis susceptibility in West African populations.
- NRAMP1 polymorphisms represent a significant genetic factor influencing tuberculosis risk.