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

Cutaneous 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. This study aimed To evaluate the association of cytotoxic T-lymphocyte antigen-4 (CTLA-4)+49G/A single nucleotide polymorphism (SNP) with incidence and severity of CL.

This 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 amplification refractory mutation- polymerase chain reaction system (TARMS-PCR) methods. Soluble CTLA-4 (sCTLA-4) was estimated in the serum using an enzyme-linked immunosorbent assay (ELISA).

The GG genotype of CTLA-4+49G/A polymorphism was significantly more common in controls than in patients (OR = 0.11, 95% CI = 0.02-0.58, p = 0.009). At allelic level, G allele was much more common in controls than in patients (30.83% vs. 17.73%) with a significant difference (OR = 2.07, 95% CI = 1.23-3.48, p = 0.006). However, there was no significant difference in the frequency of genotypes and alleles between newly diagnosed and treated patients. Median serum concentration of sCTLA-4 in newly diagnosed patients was 72.6 pg/ml (range 15.6-127 pg/ml) which was higher than either controls (median = 16.3 pg/ml, range 0.8-48.5 pg/ml) or treated patients (median = 17.9 pg/ml, range 2.9-74.7 pg/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.

Collectively, 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.