Influence of genetic variants of gamma interferon, interleukins 10 and 12 on Visceral Leishmaniasis in an endemic area, Iran

Abstract

Visceral leishmaniasis (VL) is a life threatening disease in which a variety of cytokines regulating the immune responses can determine its outcome. As based on their region in the gene, some single nucleotide polymorphisms (SNP) can influence the expression of their corresponding proteins, this study aimed to investigate the association between SNP in the IL-10, IL-12, IFN-γ genes and susceptibility to VL. The study was carried out on 120 patients with VL, 67 patients' families (family group), and 102 healthy individuals with positive leishmanin skin test as positive control group. SNPs in IL-10 (−592, −819, −1082), IL-12 (+1188) were analyzed using PCR-RFLP and allele specific polymerase chain reaction (ASPCR) was used to analyze SNPs in IFN-γ (+874 A/T). The results showed that at position +874 of IFN-γ, AT genotype was significantly more frequent in patients than that in families and controls, but TT genotype was significantly more frequent in families than in patients. Distributions of IFN-γ alleles were not significantly different between the study groups. As for IL-12 and IL-10 genotypes and alleles, no significant difference was observed between the groups. Although a strong linkage disequilibrium was observed between alleles −592, −819 and −1082 of IL-10, distributions of the most common haplotypes and haplogenotypes reconstructed from IL-10 alleles were not significantly different between the study groups. It could be suggested that heritage of AT genotype at position +874 of IFN-γ may predispose and TT genotype can resist individual to VL in an endemic area in the southwest of Iran.

Association of cytokine gene polymorphisms with susceptibility to cutaneous leishmaniasis in a Turkish population

“…To the best of our knowledge, there is no study neither in Turkey nor in other countries about the role of IL‐12 polymorphisms with CL infections. The results were similar in a few studies with VL but not CL patients 39,40 …”

“…was no association of IL-10 −1082 G/A polymorphisms with susceptibility to CL or VL. 29,30,34,39,45 We could not compare our risk estimate results with previous studies for IL-10 −1082 G/A SNP due to the deviation of HWE both in patient and control groups (Table 3).…”

“…The results were similar in a few studies with VL but not CL patients. 39,40 IL-4 plays an important role in the differentiation of naive CD4+ only in a study conducted in an Iranian population with CL patients infected with L major. IL-4 promoter −590C/T polymorphism was observed to influence disease progression and the risk of developing CL.…”

Treatment effects on IL‐9+CD4+ T cells and the cytokines influencing IL‐9 production in paediatric visceral leishmaniasis

“…This discrepancy may be due to the differences in the age, ethnic and racial diversity and the species of Lesihmania as well as the sample size. Among the ethnic and racial diversity, in a recent study, we observed that heritage of AT genotype at position + 874 of IFN‐γ corresponding to the lower level of its production is more frequent in the VL patients compared to that in the controls from an endemic area in the south west of Iran 42 …”

Cytokines: Key Determinants of Resistance or Disease Progression in Visceral Leishmaniasis: Opportunities for Novel Diagnostics and Immunotherapy

“…Reciprocal regulation is provided by the action of IL-10 on the IFN-γ producing capacity of Th1-type CD4 + T-cells (16). A recent study showed that the variation in single nucleotide polymorphisms (SNPs) of IFN-γ gene at the position +874 (A/T) influences the susceptibility to VL such that individuals in southwest of Iran with an AT genotype are susceptible and those with a TT genotype are resistant to VL (247).…”