03313nas a2200301 4500000000100000008004100001260001600042653002400058653001500082653001700097653001200114653001800126653002300144653002600167653003500193653001900228100001200247700001500259700001200274700001600286700001200302700001400314700001600328245008300344856015300427520241700580022001402997 2024 d bElsevier BV10aInfectious Diseases10aImmunology10aMicrobiology10aLeprosy10aENL Reactions10aReversal Reactions10aCC-Chemokine ligand-210aSingle nucleotide polymorphism10asusceptibility1 aKumar S1 aMohanty KK1 aSingh V1 aNatarajan M1 aArora M1 aChakma JK1 aTripathy SP00aAssociation of CC-Chemokine Ligand-2 gene Polymorphisms with Leprosy Reactions uhttps://www.sciencedirect.com/science/article/pii/S1286457924000182/pdfft?md5=96915f27ceedf76558a50ea6970c498c&pid=1-s2.0-S1286457924000182-main.pdf3 a

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 sites of inflammation. Variations in CCL2 may influence the immune response to M. 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 -2518 A>G, 535 leprosy and 290 controls for CCL2 -362 G>C, 295 leprosy and 240 controls for -2134 T>G, 325 leprosy and 288 controls for 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 {(-2518 A>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.

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