Exploring the Role of C-C Motif Chemokine Ligand-2 Single Nucleotide Polymorphism in Pulmonary Tuberculosis: A Genetic Association Study from North India
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. Th...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2020/1019639 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832566468552687616 |
|---|---|
| author | Sanjay K. Biswas Mayank Mittal Ekata Sinha Vandana Singh Nidhi Arela Bharat Bajaj Pramod K. Tiwari Vishwa M. Katoch Keshar K. Mohanty |
| author_facet | Sanjay K. Biswas Mayank Mittal Ekata Sinha Vandana Singh Nidhi Arela Bharat Bajaj Pramod K. Tiwari Vishwa M. Katoch Keshar K. Mohanty |
| author_sort | Sanjay K. Biswas |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3ac0c81f7b2246c28881565eafac9cac |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-3ac0c81f7b2246c28881565eafac9cac2025-02-03T01:03:57ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/10196391019639Exploring the Role of C-C Motif Chemokine Ligand-2 Single Nucleotide Polymorphism in Pulmonary Tuberculosis: A Genetic Association Study from North IndiaSanjay K. Biswas0Mayank Mittal1Ekata Sinha2Vandana Singh3Nidhi Arela4Bharat Bajaj5Pramod K. Tiwari6Vishwa M. Katoch7Keshar K. Mohanty8Immunology Division, National JALMA Institute for Leprosy and Other Mycobacterial Diseases (Indian Council of Medical Research), Dr Miyazaki Marg, TajGanj, 282 004, Agra, IndiaImmunology Division, National JALMA Institute for Leprosy and Other Mycobacterial Diseases (Indian Council of Medical Research), Dr Miyazaki Marg, TajGanj, 282 004, Agra, IndiaImmunology Division, National JALMA Institute for Leprosy and Other Mycobacterial Diseases (Indian Council of Medical Research), Dr Miyazaki Marg, TajGanj, 282 004, Agra, IndiaImmunology Division, National JALMA Institute for Leprosy and Other Mycobacterial Diseases (Indian Council of Medical Research), Dr Miyazaki Marg, TajGanj, 282 004, Agra, IndiaImmunology Division, National JALMA Institute for Leprosy and Other Mycobacterial Diseases (Indian Council of Medical Research), Dr Miyazaki Marg, TajGanj, 282 004, Agra, IndiaState TB Demonstration and Training Centre, Agra, IndiaDepartment of Human Genetics, Jiwaji University, Gwalior, IndiaRajasthan University of Health Sciences (RUHS), Jaipur, IndiaImmunology Division, National JALMA Institute for Leprosy and Other Mycobacterial Diseases (Indian Council of Medical Research), Dr Miyazaki Marg, TajGanj, 282 004, Agra, IndiaThe 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.http://dx.doi.org/10.1155/2020/1019639 |
| spellingShingle | Sanjay K. Biswas Mayank Mittal Ekata Sinha Vandana Singh Nidhi Arela Bharat Bajaj Pramod K. Tiwari Vishwa M. Katoch Keshar K. Mohanty Exploring the Role of C-C Motif Chemokine Ligand-2 Single Nucleotide Polymorphism in Pulmonary Tuberculosis: A Genetic Association Study from North India Journal of Immunology Research |
| title | Exploring the Role of C-C Motif Chemokine Ligand-2 Single Nucleotide Polymorphism in Pulmonary Tuberculosis: A Genetic Association Study from North India |
| title_full | Exploring the Role of C-C Motif Chemokine Ligand-2 Single Nucleotide Polymorphism in Pulmonary Tuberculosis: A Genetic Association Study from North India |
| title_fullStr | Exploring the Role of C-C Motif Chemokine Ligand-2 Single Nucleotide Polymorphism in Pulmonary Tuberculosis: A Genetic Association Study from North India |
| title_full_unstemmed | Exploring the Role of C-C Motif Chemokine Ligand-2 Single Nucleotide Polymorphism in Pulmonary Tuberculosis: A Genetic Association Study from North India |
| title_short | Exploring the Role of C-C Motif Chemokine Ligand-2 Single Nucleotide Polymorphism in Pulmonary Tuberculosis: A Genetic Association Study from North India |
| title_sort | exploring the role of c c motif chemokine ligand 2 single nucleotide polymorphism in pulmonary tuberculosis a genetic association study from north india |
| url | http://dx.doi.org/10.1155/2020/1019639 |
| work_keys_str_mv | AT sanjaykbiswas exploringtheroleofccmotifchemokineligand2singlenucleotidepolymorphisminpulmonarytuberculosisageneticassociationstudyfromnorthindia AT mayankmittal exploringtheroleofccmotifchemokineligand2singlenucleotidepolymorphisminpulmonarytuberculosisageneticassociationstudyfromnorthindia AT ekatasinha exploringtheroleofccmotifchemokineligand2singlenucleotidepolymorphisminpulmonarytuberculosisageneticassociationstudyfromnorthindia AT vandanasingh exploringtheroleofccmotifchemokineligand2singlenucleotidepolymorphisminpulmonarytuberculosisageneticassociationstudyfromnorthindia AT nidhiarela exploringtheroleofccmotifchemokineligand2singlenucleotidepolymorphisminpulmonarytuberculosisageneticassociationstudyfromnorthindia AT bharatbajaj exploringtheroleofccmotifchemokineligand2singlenucleotidepolymorphisminpulmonarytuberculosisageneticassociationstudyfromnorthindia AT pramodktiwari exploringtheroleofccmotifchemokineligand2singlenucleotidepolymorphisminpulmonarytuberculosisageneticassociationstudyfromnorthindia AT vishwamkatoch exploringtheroleofccmotifchemokineligand2singlenucleotidepolymorphisminpulmonarytuberculosisageneticassociationstudyfromnorthindia AT kesharkmohanty exploringtheroleofccmotifchemokineligand2singlenucleotidepolymorphisminpulmonarytuberculosisageneticassociationstudyfromnorthindia |