{"title":"CC-Chemokine Ligand-2 基因多态性与麻风病反应的关系","authors":"Sanjay Kumar Biswas , Keshar Kunja Mohanty , Vandana Singh , Mohan Natrajan , Mamta Arora , Joy Kumar Chakma , Srikanth Prasad Tripathy","doi":"10.1016/j.micinf.2024.105298","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p><em>C–C motif chemokine ligand 2</em>, a gene that codes for a protein involved in inflammation. Certain SNPs in the <em>CCL2</em> gene have been studied for their potential associations with susceptibility to various diseases. These SNPs may affect the production and function of the CCL2 protein, which is involved in the recruitment of immune cells to the site of inflammation. Variations in <em>CCL2</em> may influence the immune response to <em>Mycobacterium leprae</em> infection.</p></div><div><h3>Objective</h3><p>To investigate the association of the <em>C–C motif chemokine ligand-2</em> single nucleotide polymorphisms with leprosy.</p></div><div><h3>Methods</h3><p><em>CCL2</em> single nucleotide polymorphisms were analyzed in a total of 975 leprosy patients and 357 healthy controls. Of those, 577 leprosy and 288 healthy controls were analyzed by PCR-RFLP for <em>CCL2</em> -<em>2518 A</em><em>></em><em>G</em>, 535 leprosy and 290 controls for <em>CCL2</em> -362 G>C, 295 leprosy and 240 controls for <em>CCL2 -2134 T</em><em>></em><em>G</em>, 325 leprosy and 288 controls for <em>CCL2 -</em><em>1549 A</em><em>></em><em>T</em> SNPs by melting curve analysis using hybridization probe chemistry and detection by fluorescence resonance energy transfer (FRET) technique in Realtime PCR. The levels of CCL2, IL-12p70, IFN-γ, TNF-α, and TGF-β were estimated in sera samples and correlated with <em>CCL2</em> genotypes.</p></div><div><h3>Results</h3><p>The frequency of the <em>GCT</em> (-<em>2518</em> A>G, -<em>362 G</em><em>></em><em>C</em>, -<em>2134 T</em><em>></em><em>G</em>) haplotype is observed to be higher in leprosy patients compared to healthy controls (P = 0.04). There was no significant difference observed in genotypic frequencies between leprosy patients and healthy controls {(-<em>2518</em> <em>A</em><em>></em><em>G</em>, p = 0.53), (-<em>362 G</em><em>></em><em>C</em>, p = 0.01), (-<em>2134 T</em><em>></em><em>G</em>, p = 0.10)}. <em>G</em> allele at the -2134 site is predominant in leprosy (borderline) without any reaction (8 %) compared to borderline patients with RR reactions (2.1 %) (P = 0.03). <em>GG</em> genotype (p = 0.008) and <em>G</em> allele at -2518 (p = 0.030) of the <em>CCL 2</em> gene were found to be associated with patients with ENL reaction. An elevated level of serum CCL2 was observed in leprosy patients with the -<em>2518 AA</em> and <em>AG</em> genotypes (p = 0.0001).</p></div><div><h3>Conclusions</h3><p><em>G</em> allele and <em>GG</em> genotype at the <em>CCL2 -2518</em> site are associated with a risk of ENL reactions.</p></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1286457924000182/pdfft?md5=96915f27ceedf76558a50ea6970c498c&pid=1-s2.0-S1286457924000182-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Association of CC-chemokine ligand-2 gene polymorphisms with leprosy reactions\",\"authors\":\"Sanjay Kumar Biswas , Keshar Kunja Mohanty , Vandana Singh , Mohan Natrajan , Mamta Arora , Joy Kumar Chakma , Srikanth Prasad Tripathy\",\"doi\":\"10.1016/j.micinf.2024.105298\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p><em>C–C motif chemokine ligand 2</em>, a gene that codes for a protein involved in inflammation. Certain SNPs in the <em>CCL2</em> gene have been studied for their potential associations with susceptibility to various diseases. These SNPs may affect the production and function of the CCL2 protein, which is involved in the recruitment of immune cells to the site of inflammation. Variations in <em>CCL2</em> may influence the immune response to <em>Mycobacterium leprae</em> infection.</p></div><div><h3>Objective</h3><p>To investigate the association of the <em>C–C motif chemokine ligand-2</em> single nucleotide polymorphisms with leprosy.</p></div><div><h3>Methods</h3><p><em>CCL2</em> single nucleotide polymorphisms were analyzed in a total of 975 leprosy patients and 357 healthy controls. Of those, 577 leprosy and 288 healthy controls were analyzed by PCR-RFLP for <em>CCL2</em> -<em>2518 A</em><em>></em><em>G</em>, 535 leprosy and 290 controls for <em>CCL2</em> -362 G>C, 295 leprosy and 240 controls for <em>CCL2 -2134 T</em><em>></em><em>G</em>, 325 leprosy and 288 controls for <em>CCL2 -</em><em>1549 A</em><em>></em><em>T</em> SNPs by melting curve analysis using hybridization probe chemistry and detection by fluorescence resonance energy transfer (FRET) technique in Realtime PCR. The levels of CCL2, IL-12p70, IFN-γ, TNF-α, and TGF-β were estimated in sera samples and correlated with <em>CCL2</em> genotypes.</p></div><div><h3>Results</h3><p>The frequency of the <em>GCT</em> (-<em>2518</em> A>G, -<em>362 G</em><em>></em><em>C</em>, -<em>2134 T</em><em>></em><em>G</em>) haplotype is observed to be higher in leprosy patients compared to healthy controls (P = 0.04). There was no significant difference observed in genotypic frequencies between leprosy patients and healthy controls {(-<em>2518</em> <em>A</em><em>></em><em>G</em>, p = 0.53), (-<em>362 G</em><em>></em><em>C</em>, p = 0.01), (-<em>2134 T</em><em>></em><em>G</em>, p = 0.10)}. <em>G</em> allele at the -2134 site is predominant in leprosy (borderline) without any reaction (8 %) compared to borderline patients with RR reactions (2.1 %) (P = 0.03). <em>GG</em> genotype (p = 0.008) and <em>G</em> allele at -2518 (p = 0.030) of the <em>CCL 2</em> gene were found to be associated with patients with ENL reaction. An elevated level of serum CCL2 was observed in leprosy patients with the -<em>2518 AA</em> and <em>AG</em> genotypes (p = 0.0001).</p></div><div><h3>Conclusions</h3><p><em>G</em> allele and <em>GG</em> genotype at the <em>CCL2 -2518</em> site are associated with a risk of ENL reactions.</p></div>\",\"PeriodicalId\":18497,\"journal\":{\"name\":\"Microbes and Infection\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1286457924000182/pdfft?md5=96915f27ceedf76558a50ea6970c498c&pid=1-s2.0-S1286457924000182-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Microbes and Infection\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1286457924000182\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microbes and Infection","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1286457924000182","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Association of CC-chemokine ligand-2 gene polymorphisms with leprosy reactions
Background
C–C motif chemokine ligand 2, a gene that codes for a protein involved in inflammation. Certain SNPs in the CCL2 gene have been studied for their potential associations with susceptibility to various diseases. These SNPs may affect the production and function of the CCL2 protein, which is involved in the recruitment of immune cells to the site of inflammation. Variations in CCL2 may influence the immune response to Mycobacterium leprae infection.
Objective
To investigate the association of the C–C motif chemokine ligand-2 single nucleotide polymorphisms with leprosy.
Methods
CCL2 single nucleotide polymorphisms were analyzed in a total of 975 leprosy patients and 357 healthy controls. Of those, 577 leprosy and 288 healthy controls were analyzed by PCR-RFLP for CCL2 -2518 A>G, 535 leprosy and 290 controls for CCL2 -362 G>C, 295 leprosy and 240 controls for CCL2 -2134 T>G, 325 leprosy and 288 controls for CCL2 -1549 A>T SNPs by melting curve analysis using hybridization probe chemistry and detection by fluorescence resonance energy transfer (FRET) technique in Realtime PCR. The levels of CCL2, IL-12p70, IFN-γ, TNF-α, and TGF-β were estimated in sera samples and correlated with CCL2 genotypes.
Results
The frequency of the GCT (-2518 A>G, -362 G>C, -2134 T>G) haplotype is observed to be higher in leprosy patients compared to healthy controls (P = 0.04). There was no significant difference observed in genotypic frequencies between leprosy patients and healthy controls {(-2518A>G, p = 0.53), (-362 G>C, p = 0.01), (-2134 T>G, p = 0.10)}. G allele at the -2134 site is predominant in leprosy (borderline) without any reaction (8 %) compared to borderline patients with RR reactions (2.1 %) (P = 0.03). GG genotype (p = 0.008) and G allele at -2518 (p = 0.030) of the CCL 2 gene were found to be associated with patients with ENL reaction. An elevated level of serum CCL2 was observed in leprosy patients with the -2518 AA and AG genotypes (p = 0.0001).
Conclusions
G allele and GG genotype at the CCL2 -2518 site are associated with a risk of ENL reactions.
期刊介绍:
Microbes and Infection publishes 10 peer-reviewed issues per year in all fields of infection and immunity, covering the different levels of host-microbe interactions, and in particular:
the molecular biology and cell biology of the crosstalk between hosts (human and model organisms) and microbes (viruses, bacteria, parasites and fungi), including molecular virulence and evasion mechanisms.
the immune response to infection, including pathogenesis and host susceptibility.
emerging human infectious diseases.
systems immunology.
molecular epidemiology/genetics of host pathogen interactions.
microbiota and host "interactions".
vaccine development, including novel strategies and adjuvants.
Clinical studies, accounts of clinical trials and biomarker studies in infectious diseases are within the scope of the journal.
Microbes and Infection publishes articles on human pathogens or pathogens of model systems. However, articles on other microbes can be published if they contribute to our understanding of basic mechanisms of host-pathogen interactions. Purely descriptive and preliminary studies are discouraged.