Serum iron levels in tuberculosis patients and household contacts and its association with natural resistance‐associated macrophage protein 1 polymorphism and expression

Author:

Waworuntu Wiendra12,Tanoerahardjo Francisca Srioetami2,Mallongi Anwar3,Ahmad Ahyar4,Amin Muhammad5,Djaharuddin Irawaty67,Bukhari Agussalim8,Tabri Nur Ahmad67,Bahar Burhanuddin9,Hidayah Najdah10ORCID,Halik Handayani211,Massi Muhammad Nasrum1112ORCID

Affiliation:

1. Pusat Kebijakan Sumber Daya dan Sistem Ketahanan Kesehatan, Badan Kebijakan Pembangunan Kesehatan Ministry of Health Republic Indonesia Jakarta Indonesia

2. Postgraduate Program, Faculty of Medicine, Universitas Hasanuddin Makassar South Sulawesi Indonesia

3. Department of Environmental Health, Faculty of Public Health Universitas Hasanuddin Makassar South Sulawesi Indonesia

4. Department of Chemistry, Faculty of Mathematics and Natural Sciences Universitas Hasanuddin Makassar South Sulawesi Indonesia

5. Department of Pulmonology and Respiratory Diseases, Faculty of Medicine Universitas Airlangga Surabaya West Java Indonesia

6. Department of Pulmonology and Respiratory Diseases, Faculty of Medicine Universitas Hasanuddin Makassar South Sulawesi Indonesia

7. Dr. Wahidin Sudirohusodo Hospital Makassar South Sulawesi Indonesia

8. Department of Clinical Nutrition, Faculty of Medicine Universitas Hasanuddin Makassar South Sulawesi Indonesia

9. Department of Nutrition Sciences, Faculty of Public Health Hasanuddin University Makassar Indonesia

10. Research Center for Vaccine and Drugs National Research and Innovation Agency (BRIN) Tangerang Selatan Banten Indonesia

11. Hasanuddin University Medical Research Center Laboratory, Faculty of Medicine Universitas Hasanuddin Makassar South Sulawesi Indonesia

12. Department of Clinical Microbiology, Faculty of Medicine Universitas Hasanuddin Makassar South Sulawesi Indonesia

Abstract

AbstractBackgroundIron deficiency can impair immune function, increasing tuberculosis (TB) susceptibility and severity. The research aimed to investigate iron deficiency anemia in TB patients and household contacts and its association with natural resistance‐associated macrophage protein 1 (NRAMP1) polymorphism and expression.MethodsThe levels of iron, ferritin, and transferrin were measured in the serum by ELISA (Enzyme‐Linked Immunosorbent Assay). NRAMP1 polymorphisms were determined by polymerase chain reaction (PCR) and sequencing. NRAMP1 gene expression was measured by real‐time PCR. Interferon‐gamma release assay (IGRA) checked on household contacts to screen household contacts with positive IGRA as the control.ResultsThis study involved 35 TB cases and 35 TB contacts. The results showed that the serum Fe levels were found to be lower in the TB case group (median 149.6 μmol/L) than in the positive IGRA household contacts group (median 628.53 μmol/L) with a p‐value <0.001. Meanwhile, ferritin levels in TB cases tended to be higher, in contrast to transferrin, which was found to tend to be lower in TB cases than household contacts but did not show a significant difference. This study found no association between the polymorphism of exon 15 D543 and active TB. However, NRAMP1 gene expression was lower in TB cases than in positive IGRA household contacts (p = 0.011). Besides, there was a positive correlation between NRAMP1 gene expression and serum Fe levels (r = 0.367, p = 0.006). TB was associated with decreased NRAMP1 gene expression (OR 0.086 95% CI 0.02–0.366, p = 0.001). Besides, TB was associated with low Fe levels (OR 0.533 95% CI 0.453–0.629, p < 0.001).ConclusionComparing the TB case to the household contacts group, decreased serum Fe levels were discovered in the TB case group. This study also shows a correlation of NRAMP1 gene expression to Fe levels in TB patients and household contacts and describes that TB may lead to decreased Fe levels by downregulating NRAMP1 expression.

Publisher

Wiley

Subject

Genetics (clinical),Pulmonary and Respiratory Medicine,Immunology and Allergy

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