# Nitric Oxide Synthase 2 (NOS2) Gene Polymorphisms Association With Risk of Pulmonary Tuberculosis (PTB): A Case‐Control Study

**Authors:** Ebrahim Alijani, Mahboobeh Sabeti Akbar-Abad, Hossein Shahriari, Fatemeh Keykha, Mahdi Majidpour, Michael Faqih, Mohsen Taheri, Mahdi Atabaki

PMC · DOI: 10.1155/bmri/6656158 · BioMed Research International · 2026-02-25

## TL;DR

This study explores how genetic variations in the NOS2 gene affect the risk of developing pulmonary tuberculosis.

## Contribution

The study identifies specific NOS2 gene polymorphisms associated with increased or decreased PTB risk in a case-control design.

## Key findings

- rs2297518 and rs1800482 polymorphisms were associated with reduced PTB risk in multiple genetic models.
- rs9282799 polymorphism was linked to increased PTB risk in several genetic models.
- NOS2 gene variations may influence immune response to Mycobacterium tuberculosis.

## Abstract

Pulmonary tuberculosis (PTB) remains a significant global health challenge, necessitating a deeper understanding of genetic factors influencing susceptibility. This study investigates the association between five specific polymorphisms in the nitric oxide synthase 2 (NOS2) genes (rs7215373, rs2297518, rs2274894, rs1800482, and rs9282799) and the risk of developing PTB.

Utilizing a case‐control design, we analyzed genetic samples from 150 PTB patients and 150 matched healthy controls. Genotyping was conducted using amplification refractory mutation system‐polymerase chain reaction (ARMS‐PCR) methods. Statistical analyses, including logistic regression and Hardy–Weinberg equilibrium tests, were performed to assess the associations between NOS2 polymorphisms and PTB risk.

Our findings indicate that the rs7215373 and rs2274894 polymorphisms had no significant association with the risk of PTB. rs2297518 in the allelic model significantly reduced the risk by 0.50 against the occurrence of PTB (p = 0.041). rs1800482 polymorphism in the Codominant 2 (p = 0.041), recessive (p = 0.043), and allelic (p = 0.007) models reduced the risk of PTB by 0.85, 0.80, and 0.75, respectively. However, our results in examining the rs9282799 polymorphism showed that, contrary to previous results, the Codominant 1 (p = 0.009), dominant (p = 0.005), overdominant (p = 0.012), and allelic (p = 0.004) models increased the risk of PTB by 3.80, 3.75, 3.78, and 3.49, respectively.

These results suggest that specific NOS2 gene polymorphisms may play a role in modulating the immune response to Mycobacterium tuberculosis, highlighting their potential as biomarkers for PTB risk assessment. Further research is warranted to elucidate the underlying mechanisms and to explore the implications for targeted prevention strategies in high‐risk populations.

## Linked entities

- **Genes:** NOS2 (nitric oxide synthase 2) [NCBI Gene 4843]
- **Diseases:** Pulmonary tuberculosis (MONDO:0006052)

## Full-text entities

- **Genes:** IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, NOS2 (nitric oxide synthase 2) [NCBI Gene 4843] {aka HEP-NOS, INOS, NOS, NOS2A}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** infectious disease (MESH:D003141), TB (MESH:D014390), Mtb infection (MESH:D014376), chronic hepatitis B (MESH:D019694), weight loss (MESH:D015431), cough (MESH:D003371), neurovascular disorder (MESH:D013901), COVID-19 (MESH:D000086382), infection (MESH:D007239), PTB (MESH:D014397), bronchiectasis (MESH:D001987), fever (MESH:D005334), hemoptysis (MESH:D006469), chronic obstructive pulmonary disease (MESH:D029424), asthma (MESH:D001249), lung cancer (MESH:D008175), respiratory illnesses (MESH:D012140), cervical cancer (MESH:D002583), inflammation (MESH:D007249)
- **Chemicals:** agarose (MESH:D012685), lipids (MESH:D008055), L-arginine (MESH:D001120), RNIs (-), NO (MESH:D009569), water (MESH:D014867), EDTA (MESH:D004492)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mycobacterium tuberculosis (species) [taxon 1773]
- **Mutations:** rs9282799, rs7215373, rs1800482, C/T, 26128581 C> a, G/T, G/A, rs2274894, rs2297518, C/G, Rs2779249

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## References

41 references — full list in the complete paper: https://tomesphere.com/paper/PMC12935765/full.md

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Source: https://tomesphere.com/paper/PMC12935765