Toll-like receptor 2 (-196 to -174) del and TLR1 743 A > G gene polymorphism-a possible association with drug-resistant tuberculosis in the north Indian population

Deepika Varshney; Shoor Vir Singh; Keshar Kunja Mohanty; Santosh Kumar; Nitin Varshney; Ekata Sinha; Sushanta Kumar Barik

doi:10.3389/fmicb.2023.1305974

Toll-like receptor 2 (-196 to -174) del and TLR1 743 A > G gene polymorphism-a possible association with drug-resistant tuberculosis in the north Indian population

Front Microbiol. 2024 Jan 24:14:1305974. doi: 10.3389/fmicb.2023.1305974. eCollection 2023.

Authors

Deepika Varshney¹, Shoor Vir Singh², Keshar Kunja Mohanty¹, Santosh Kumar³, Nitin Varshney⁴, Ekata Sinha¹, Sushanta Kumar Barik¹

Affiliations

¹ ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, Uttar Pradesh, India.
² Department of Biotechnology, Institute of Applied Sciences & Humanities, GLA University, Mathura, Uttar Pradesh, India.
³ Department of Chest and Tuberculosis, S. N. Medical College & Hospital, Agra, Uttar Pradesh, India.
⁴ Department of Agricultural Statistics and Computer Centre, N. M. College of Agriculture, Navsari Agricultural University, Navsari, Gujarat, India.

Abstract

Objectives: The objective of this study is to analyze the association between TLR2 deletion (-196 to -174) and TLR1 743 A > G gene polymorphism with drug resistant tuberculosis (PTB, MDR-TB, and XDR-TB) in a population from Agra, Uttar Pradesh.

Methods: The present case-control study included 101 pulmonary TB patients, 104 multidrug-resistant TB patients, 48 extremely drug-resistant TB patients, and 130 healthy and unrelated controls residing in the same locality. The genotyping method for TLR2 deletion (-196 to -174) was carried out by allele-specific polymerase chain reaction (PCR), and TLR1 743 A > G gene polymorphism was performed by hybridization probe chemistry in Roche Real-Time PCR. Genotype and allele frequencies were analyzed by the chi-square test. Cytokine levels were measured by ELISA and compared using Mann-Whitney and Kruskal-Wallis tests.

Results: The frequency of heterozygous (Ins/del) genotypes for TLR2 (-196 to -174) polymorphism was predominant in XDR-TB patients (0.57), whereas heterozygous A/G genotype for TLR1 743 A > G single nucleotide polymorphism (SNP) was predominant in healthy controls (0.57) for TLR1 743 A > G gene polymorphism. The heterozygous genotype of TLR2 deletion polymorphism was found to be significantly higher in XDR-TB (p = 0.0001). TLR1 743 A > G SNP, AG genotypes were found to be significantly associated with healthy controls than PTB (p = 0.047). The level of serum cytokines (IL-6, TNF-α, and IFN-γ) was also found to be significantly different among TB patients and healthy controls.

Conclusion: The findings suggested that in the present population, the heterozygous (Ins/Del) genotype and deletion allele of TLR2 deletion (-196 to -174) polymorphism are associated with the risk for the development of drug-resistant TB. Furthermore, for TLR1 743 A > G gene polymorphism, A/G genotype, and G allele are found associated with healthy controls, suggesting the protective role against TB.

Keywords: IFN-γ; IL-6; TNF-α; Toll-like receptors; drug-resistant tuberculosis; genotyping.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study is funded by intramural research funding of ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra. Raj Pal Suman is acknowledged for technical help. DV was financially supported as PhD scholar by the Department of Science and Technology (DST), New Delhi (Award letter code. IF180309).