Exploring the Role of C-C Motif Chemokine Ligand-2 Single Nucleotide Polymorphism in Pulmonary Tuberculosis: A Genetic Association Study from North India
| Autor: | Mayank Mittal, Bharat Bajaj, Ekata Sinha, Vishwa M. Katoch, Nidhi Arela, Sanjay Kumar Biswas, Vandana Singh, Keshar Kunja Mohanty, Pramod Kumar Tiwari |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Male Article Subject Adolescent Genotype Immunology Population India Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide 03 medical and health sciences Young Adult 0302 clinical medicine Gene Frequency Immunology and Allergy Humans Genetic Predisposition to Disease Allele education Allele frequency Genotyping Tuberculosis Pulmonary Alleles Chemokine CCL2 Genetic Association Studies Genetic association education.field_of_study Haplotype General Medicine Mycobacterium tuberculosis RC581-607 Middle Aged Molecular biology 030104 developmental biology Haplotypes Case-Control Studies Population Surveillance Cytokines Female Immunologic diseases. Allergy 030215 immunology Research Article |
| Zdroj: | Journal of Immunology Research Journal of Immunology Research, Vol 2020 (2020) |
| ISSN: | 2314-7156 |
| Popis: | The C-C motif chemokine ligand-2 (CCL2) was evidenced to be associated with tuberculosis susceptibility in some ethnic groups. In the present study, effort was made to find out the association of CCL2-2518 A>G and -362 G>C variants with susceptibility to TB in a population from North India. The genotyping was carried out in 373 participants with pulmonary TB (PTB) and 248 healthy controls (HCs) for CCL2-2518 A>G and -362 G>C polymorphisms by PCR-RFLP and by melting curve analysis using fluorescence-labeled hybridization fluorescent resonance energy transfer (FRET) probes, respectively, followed by DNA sequencing in a few representative samples. Genotype and allele frequencies were compared by the chi-squared test and crude and Mantel-Haenszel (M-H) odds ratio (OR). OR was calculated using STATA/MP16.1 software. Further, CCL2, IL-12p70, IFN-γ, TNF-α, and TGF-β levels were measured in serum samples of these participants using commercially available kits. Our analysis indicated that the homozygous mutant in both -2518 GG ( OR = 2.07 , p = 0.02 ) and -362 CC ( OR = 1.92 , p = 0.03 ) genotypes was associated with susceptibility to pulmonary TB. Further, heterozygous genotypes -2518AG ( OR = 0.60 , p = 0.003 ) and -362GC ( OR = 0.64 , p = 0.013 ) provide resistance from PTB disease. Haplotype analysis revealed AC haplotype ( p = 0.006 ) to be a risk factor associated with PTB susceptibility. The serum CCL2 level was significantly elevated among participants with -2518 AA genotype compared to -2518 GG genotype. CCL2 level was observed to be positively correlated with IL12p70, IFN-γ and TNF-α, thus suggesting the immunological regulatory role of CCL2 against pulmonary tuberculosis. CCL2-2518 GG and -362 CC genotypes were found to be associated with susceptibility to pulmonary tuberculosis and CCL2-2518AG and CCL2-362GC with resistance from PTB. AC haplotype was found to be a risk factor for PTB in the present study. It may be hypothesized from the findings that -2518G allele could be responsible for lower production of CCL2 which leads to defective Th1 response and makes a host susceptible for pulmonary tuberculosis. |
| Databáze: | OpenAIRE |
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