Variants of the SFTPA1 and SFTPA2 genes and susceptibility to tuberculosis in Ethiopia |
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| Authors: | S. Malik C.M.T. Greenwood T. Eguale A. Kifle J. Beyene A. Habte A. Tadesse H. Gebrexabher S. Britton E. Schurr |
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| Affiliation: | (1) McGill Centre for the Study of Host Resistance and Departments of Medicine and Human Genetics, McGill University, Montreal, QC, Canada;(2) Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto, ON, Canada;(3) Armauer Hansen Research Institute, Addis Ababa, Ethiopia;(4) Department of Medicine at Karolinska Hospital, Unit of Infectious Diseases, Huddinge, Stockholm, Sweden;(5) Research Institute of the Montreal General Hospital, Rm L11-520, 1650 Cedar Avenue, H3G 1A4 Montreal, QC, Canada |
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| Abstract: | Lungs are the central organ affected and targeted by Mycobacterium tuberculosis and immune processes in the lung are of critical importance in the pathogenesis of tuberculosis. A major lung defense against invading pathogens is provided by surfactant protein A, a multi-chain protein encoded by the SFTPA1 and SFTPA2 genes. Here, we investigated polymorphisms in the SFTPA1 and SFTPA2 genes for association with tuberculosis in 181 Ethiopian families comprising 226 tuberculosis cases. Four polymorphisms, SFTPA1 307A, SFTPA1 776T, SFTPA2 355C, and SFTPA2 751C, were associated with tuberculosis (P=0.00008; P=0.019, P=0.029 and P=0.042, respectively). Additional subgroup analysis in male, female and more severely affected patients provided evidence for SFTPA1/2-covariate interaction. Finally, out of five intragenic haplotypes identified in the SFTPA1 gene and nine identified in the SFTPA2 gene, 1A 3 was most significantly associated with tuberculosis susceptibility (P=0.026). These findings suggest that SFTPA1 and SFTPA2 modify the risk of tuberculosis susceptibility and that this risk is influenced by additional covariates. |
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| Keywords: | Tuberculosis Complex trait Candidate gene Innate immunity |
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