Cytokines signatures and susceptibility to cutaneous leishmaniasis in patients from Sistan and Baluchestan province of Iran

• Published in: Gene Vol. 903; p. 148224
• Main Authors: Jahanshahi, Saeideh, Nejad, Hamideh Rouhani, Kazemi, Bahram, Saeedi, Pardis
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.04.2024
• Subjects: Cutaneous leishmaniasis; Cytokine; DNA; gene frequency; genes; genetic polymorphism; genotype; Genotyping; interleukin-10; Iran; Leishmania; microscopy; parasites; Phlebotominae; Single nucleotide polymorphism (SNP); Iran; Cutaneous leishmaniasis; ORs; Genotyping; SNP; Cytokine; ITS2; CL; Cis; Single nucleotide polymorphism (SNP); ML; cutaneous leishmaniasis; Single Nucleotide Polymorphism (SNP)
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2024.148224

•Certain cytokine gene polymorphisms associate with cutaneous leishmaniasis (CL) susceptibility.•Significant differences exist between CL patients and endemic controls for TGF-β1, IFN-γ, and IL-10 variants.•The TGF-β1 (rs1800469) SNP links to over 5-fold greater CL risk in southeastern Iran.•IFN-γ (rs2430561) AA genotype demonstrates a 4-fold increased frequency in CL cases.•A nearly 2-fold heightened risk occurs with the IL-10 (rs1800871) CC genotype among patients. Cutaneous leishmaniasis (CL) is a complex, multifactorial disease that results from environmental factors such as parasite polymorphism, phlebotomine vectors, and host genetic factors. Some studies have identified specific genetic factors that may be associated with cutaneous leishmaniasis. The objective of this research was to resolve the association of 8 cytokine polymorphisms, including TNF-α −308 A/G (rs 1800629), TNF-α −238 A/G (rs 361525), TGF-β1 −509 T/C (rs 1800469), TGF-β1+ 915 G/C (rs 1800471), IFN-γ −874 T/A (rs 2430561), IFN-γ −179 G/A (rs 2069709), IL-10 −819 C/T (rs 1800871), and IL-10 −592 A/C (rs 1800872) with susceptibility to CL. A total of 152 patients with designated CL and 100 healthy controls were selected from those referred to Sistan and Baluchestan hospitals. CL was diagnosed by microscopic examination of Giemsa-stained samples and culture. Leishmania species were identified using ITS2 gene PCR amplification with universal primers. Genetic polymorphism was determined by the ARMS PCR method on extracted genomic DNA of individuals. Eight SNPs cytokines were genotyped. Most of the Genotypic and allelic frequency comparisons between patients with CL and healthy subjects showed no difference, except 3. Individual SNP analysis showed highest association of TGF-β1 −509 (rs1800469) –CC genotype (P = 0.03, OR = 7.05, 95 % CI = 3.3–15) with 5.7-fold increase, IFN-γ −874 (rs 2430561) -AA genotype (P = 0.04, OR = 4.72, 95 % CI = 1.6–14) with 4.2-fold increase, and IL10 −819 (rs1800871) –CC genotype (P = 0.05, OR = 3.63, 95 % CI = 2.5–5.3) with 1.9-fold increase, with CL. Odds ratios (ORs) and 95 % confidence intervals (CIs) were evaluated to assess the association power. Our results conclude that rs1800469 (TGF-β1), rs2430561 (INF-γ), and rs1800872 (IL10) polymorphisms are associated with CL in southeastern Iranian people.