AUTHOR=Varshney Deepika , Singh Shoor Vir , Mohanty Keshar Kunja , Kumar Santosh , Varshney Nitin , Sinha Ekata , Barik Sushanta Kumar 

TITLE=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

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1305974

DOI=10.3389/fmicb.2023.1305974

ISSN=1664-302X

ABSTRACT=<sec id="sec1"><title>Objectives</title><p>The objective of this study is to analyze the association between <italic>TLR2 deletion (−196 to −174)</italic> and <italic>TLR1 743 A &gt; G</italic> gene polymorphism with drug resistant tuberculosis (PTB, MDR-TB, and XDR-TB) in a population from Agra, Uttar Pradesh.</p></sec><sec id="sec2"><title>Methods</title><p>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 <italic>TLR2 deletion (−196 to −174)</italic> was carried out by allele-specific polymerase chain reaction (PCR), and <italic>TLR1 743 A &gt; G</italic> 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.</p></sec><sec id="sec3"><title>Results</title><p>The frequency of heterozygous (<italic>Ins/del</italic>) genotypes for <italic>TLR2 (−196 to −174)</italic> polymorphism was predominant in XDR-TB patients (0.57), whereas heterozygous A/G genotype for <italic>TLR1 743 A &gt; G</italic> single nucleotide polymorphism (SNP) was predominant in healthy controls (0.57) for <italic>TLR1 743 A &gt; G</italic> gene polymorphism. The heterozygous genotype of <italic>TLR2 deletion</italic> polymorphism was found to be significantly higher in XDR-TB (<italic>p</italic> = 0.0001). <italic>TLR1 743 A &gt; G</italic> SNP, AG genotypes were found to be significantly associated with healthy controls than PTB (<italic>p</italic> = 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.</p></sec><sec id="sec4"><title>Conclusion</title><p>The findings suggested that in the present population, the heterozygous (<italic>Ins/Del</italic>) genotype and deletion allele of <italic>TLR2 deletion (−196 to −174)</italic> polymorphism are associated with the risk for the development of drug-resistant TB. Furthermore, for <italic>TLR1 743 A &gt; G</italic> gene polymorphism, A/G genotype, and G allele are found associated with healthy controls, suggesting the protective role against TB.</p></sec>