Ethnic-specific genetic associations with pulmonary tuberculosis.
Several susceptibility-associated genetic polymorphisms have been proposed to explain differential susceptibility to tuberculosis (TB) disease progression in different populations. Here, polymorphisms in the natural resistance-associated macrophage protein 1 (NRAMP1), vitamin D receptor, tumor necrosis factor-alpha, interleukin (IL)-1, and IL-10 genes were evaluated in 358 Cambodian patients with pulmonary TB and 106 tuberculin-positive control subjects. Heterozygosity for the -1082 polymorphism of the IL-10 promoter and heterozygosity for 2 linked polymorphic NRAMP1 variants, D543N and 3' untranslated region, were associated with TB susceptibility and resistance, respectively. Other polymorphisms associated with differential susceptibility to TB were not associated with susceptibility or resistance to TB in Cambodians. The novel pattern of genetic associations with susceptibility and resistance to TB detected in Cambodia is consistent with the conclusion that unique environmental and natural selective factors have resulted in the development of ethnic-specific host genetic factors associated with TB susceptibility and resistance worldwide.
Delgado
Julio C
JC
Center for Blood Research and Departments of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Baena
Andres
A
Thim
Sok
S
Goldfeld
Anne E
AE
D000328:Adult; D027682:Cation Transport Proteins / Q000235:genetics; D004198:Disease Susceptibility; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics; D014397:Tuberculosis, Pulmonary / Q000208:ethnology / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D007375:Interleukin-1; D016753:Interleukin-10; D018167:Receptors, Calcitriol; D014409:Tumor Necrosis Factor-alpha; D000099173:Natural Resistance-associated Macrophage Protein 1