The role of cytotoxic T-Lymphocyte antigen-4+49A/G gene polymorphism in cutaneous leishmaniasis.

Abstract

BACKGROUND\nCutaneous Leishmaniasis (CL) is a parasitic disease caused by intracellular protozoa belonging to the Leishmania genus. In endemic areas, only a proportion of exposed subjects develop the disease under almost similar circumstances, reflecting the role of genetic inheritance in resistance and susceptibility to infection. To evaluate the association of cytotoxic T-lymphocyte antigen-4 (CTLA-4)+49G/A single nucleotide polymorphism (SNP) with incidence and severity of CL.\n\n\nMETHODS\nThis cross-sectional study includes 110 patients with confirmed CL (60 newly diagnosed and 50 patients undergoing treatment) and 60 healthy subjects of similar age and sex. The CTLA-4 gene fragment corresponding to CTLA-4+49G/A polymorphism was amplified and genotyped using tetra primer refractory mutation of the polymerase chain reaction system (T ARMS PCR) methods. Soluble CTLA-4 (sCTLA-4) was estimated in the serum using an enzyme-linked immunosorbent assay (ELISA).\n\n\nRESULTS\nThe GG genotype of CTLA-4+49G/A polymorphism was more common in controls than in patients with significant differences (OR\xa0=\xa00.11, 95% CI\xa0=\xa00.02-0.58, p\xa0=\xa00.009). At allelic level, G allele was much more common in controls than in patients (30.83% vs. 17.73%) with a significant difference (OR\xa0=\xa02.07, 95% CI\xa0=\xa01.23-3.48, p\xa0=\xa00.006). However, there was no significant difference in the frequency of genotypes and alleles in newly diagnosed and treated patients. Median serum concentration of sCTLA-4 in newly diagnosed patients was 72.6\xa0pg/ml (range 15.6-127\xa0pg/ml) which was higher than either controls (median\xa0=\xa016.3\xa0pg/ml, range 0.8-48.5\xa0pg/ml) or treated patients (median\xa0=\xa017.9\xa0pg/ml, range 2.9-74.7\xa0pg/ml) with highly significant differences, while there was no significant difference between controls and treated patients. The median sCTLA-4 level was comparable across genotypes of the CTLA-4+49G/A polymorphism, with no significant difference.\n\n\nCONCLUSIONS\nCollectively, these results show the protective role of allele G of the SNP CTLA-4+49G/A against CL and increased serum sCTLA-4 in newly diagnosed CL patients, which may be used as an additional diagnostic tool. Different genotypes of the CTLA-4+49G/A polymorphism have no effect on sCLTA-4 serum levels.