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SLC11A1 genetic variation and low expression may cause immune response impairment in TB patients

Genes & Immunity volume 23, pages 85–92 (2022)Cite this article

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Abstract

Tuberculosis (TB) is caused by Mycobacterium tuberculosis. Host genetic factors are important for the detection of TB susceptibility. SLC11A1 is located in monocyte phagolysosomes that help to limit M. tuberculosis growth by transferring divalent cations across the membrane. Genetic variation in SLC11A1 may alter its expression and increase the susceptibility of individuals to TB. The current study aimed to provide insight into host genetic variations and gene expression in TB patients. A total of 164 TB patients and 85 healthy controls were enrolled in this study. SLC11A1 polymorphisms were detected by PCR-RFLP. Real-time qPCR was used for SLC11A1 gene expression, and ELISA was used for protein estimation. GTEx Portal was used for quantitative trait loci analysis, while the STRING (v.11) web platform was used for gene interactive network construction. Data were analyzed using SPSS, GraphPad Prism, Haploview, and SNPstats. SLC11A1 polymorphisms and combinatorial genotypes were strongly associated with TB susceptibility, which may explain the greater prevalence of tuberculosis in the local population. Polymorphisms in SLC11A1 have also been linked to gene expression variation. Furthermore, the expression of SLC11A1 was downregulated in TB patients, which may influence the function of other associated genes and may impair the immunological response to tuberculosis.

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Fig. 1: SLC11A1 PCR-RFLP analysis for polymorphism.
Fig. 2: SLC11A1 linkage disequilibrium, quantitative trait loci, and gene interaction network analysis.
Fig. 3: SLC11A1 gene expression and serum level in TB patients and healthy controls.

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Acknowledgements

We sincerely acknowledge the University of Health Sciences Lahore for supporting this study.

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Authors and Affiliations

  1. Department of Immunology, University of Health Sciences, Lahore, Pakistan

    Faheem Shahzad, Atia Ali, Ali Ammar, Mohammad Kashif, Khursheed Javaid, Shah Jahan, Romeeza Tahir & Nadeem Afzal

  2. Department of Livestock Management, Agriculture University Faisalabad, Faisalabad, Pakistan

    Noman Bashir

  3. Continental Medical College, Lahore, Pakistan

    Ayesha Nadeem

  4. Ameer-Ud-Din Medical College, Lahore, Pakistan

    Muhammad Rizwan

  5. Services Institute of Medical Sciences, Lahore, Pakistan

    Abid Mushtaq

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  1. Faheem Shahzad
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Contributions

FS contributed by conceiving, planning, and designing the work, acquiring, analyzing, and interpreting the data, writing and submitting the work. NB contributed by acquiring, drafting, and revising the work. AtA and AN contributed by acquiring, analyzing, and interpreting the data. AAm contributed by analyzing and interpreting the data and revising the work. MK contributed by acquiring the data and by revising the work. KJ contributed by acquiring the data and by revising the work. SJ contributed by conceiving and designing the work, by analyzing and interpreting the data and supervising the work. RT contributed by designing, drafting and revising the work. MR contributed by designing the work and analyzing the data. AM contributed by acquiring and analyzing the data. NA contributed by conceiving and designing the work, by analyzing and interpreting the data, revising and approving the final draft and supervising the overall work.

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Correspondence to Faheem Shahzad.

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Shahzad, F., Bashir, N., Ali, A. et al. SLC11A1 genetic variation and low expression may cause immune response impairment in TB patients. Genes Immun 23, 85–92 (2022). https://doi.org/10.1038/s41435-022-00165-9

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