Genetic Polymorphisms in Cytokine Genes in Colombian Patients with Ocular Toxoplasmosis

Abstract

Toxoplasmosis is caused by infection with the protozoan parasite , which has the capacity to infect all warm-blooded animals worldwide. Toxoplasmosis is a major cause of visual defects in the Colombian population; however, the association between genetic polymorphisms in cytokine genes and susceptibility to ocular toxoplasmosis has not been studied in this population. This work evaluates the associations between polymorphisms in genes coding for the cytokines tumor necrosis factor alpha (TNF-α) (rs1799964, rs1800629, rs1799724, rs1800630, and rs361525), interleukin 1β (IL-1β) (rs16944, rs1143634, and rs1143627), IL-1α (rs1800587), gamma interferon (IFN-γ) (rs2430561), and IL-10 (rs1800896 and rs1800871) and the presence of ocular toxoplasmosis (OT) in a sample of a Colombian population (61 patients with OT and 116 healthy controls). Genotyping was performed with the "dideoxynucleotide (ddNTP) primer extension" technique. Functional-effect predictions of single nucleotide polymorphisms (SNPs) were done by using FuncPred. A polymorphism in the IL-10 gene promoter (-1082G/A) was significantly more prevalent in OT patients than in controls ( = 1.93e-08; odds ratio [OR] = 5.27e+03; 95% confidence interval [CI] = 3.18 to 8.739; Bonferroni correction [BONF] = 3.48e-07). In contrast, haplotype "AG" of the IL-10 gene promoter polymorphisms (rs1800896 and rs1800871) was present at a lower frequency in OT patients ( = 7e-04; OR = 0.10; 95% CI = 0.03 to 0.35). The +874A/T polymorphism of IFN-γ was associated with OT ( = 3.37e-05; OR = 4.2; 95% CI = 2.478 to 7.12; BONF = 6.07e-04). Haplotype "GAG" of the IL-1β gene promoter polymorphisms (rs1143634, rs1143627, and rs16944) appeared to be significantly associated with OT ( = 0.0494). The IL-10, IFN-γ, and IL-1β polymorphisms influence the development of OT in the Colombian population.

Influence of Two Major Toxoplasma Gondii Virulence Factors (ROP16 and ROP18) on the Immune Response of Peripheral Blood Mononuclear Cells to Human Toxoplasmosis Infection

“…Regarding the IFN-γ promoter (SNP rs2430561) polymorphism, we found that individuals with the T/T genotype produced higher levels of IFN-γ than those with T/A alleles. This results are in agreement with the findings from previous studies (De Albuquerque et al, 2009; Neves et al, 2013; Naranjo-Galvis et al, 2018) where the A-allele was found to enhance susceptibility to OT, and also shown the importance of host genetics in terms of IFN-γ secretion in the anti-parasite response. The T/T genotype has previously been reported to be associated with protection against the retinochoroiditis caused by toxoplasmosis (De Albuquerque et al, 2009).…”

“…The next question we addressed was whether polymorphisms in the host's immune system-related genes were associated with differences in cytokine secretion from the PBMCs infected with T. gondii . We investigated this because during toxoplasmosis infection, polymorphisms in both IFN-γ (rs2430561) and IL-10 (rs1800871) and the “GAG” haplotype in the IL-1β gene's promoter (SNPs at rs1143634, rs1143627, rs16944) are associated with the development of OT in the Colombian population (Naranjo-Galvis et al, 2018). Regarding the IFN-γ promoter (SNP rs2430561) polymorphism, we found that individuals with the T/T genotype produced higher levels of IFN-γ than those with T/A alleles.…”

“…Amplification products were analyzed by capillary electrophoresis. The mini-sequencing technique or “ddNTP primer extension” was used as previously reported (Naranjo-Galvis et al, 2018). Briefly, after genomic DNA was isolated from blood cells using the QIAGEN DNA mini kit (QIAGEN), the SNP-containing regions of interest were PCR-amplified using initiation primers.…”

Pathophysiology of ocular toxoplasmosis: Facts and open questions

“…As there are only very few animal studies using these atypical strains [ 98 ], the pathophysiology of these infections is still largely unknown. Interestingly, human genetic disposition, mainly concerning immune response genes, also seems to be an important factor to determine the development of severe disease [ 99 ]. The high frequency of pathological cases in South America surely will result in more interesting human studies regarding genetic predisposition.…”

Association between Interleukin-10 Gene Polymorphisms and Behcet’s Disease Susceptibility: Evidence from a Meta-Analysis

“…Previous studies had demonstrated that these three polymorphisms were proposed to affect the transcription efficiency and expression of the IL-10 gene [41]. More than 70% of the individual variability in human IL-10 production has been attributed to genetic variation, which could help to predict patient susceptibility to the disease as well as the severity and progression of the disease [42][43][44]. For the -1082A>G polymorphism, the A allele demonstrated a higher binding affinity to the transcription factor PU.1, resulting in decreased transcriptional activity and lower expression level of IL-10 [45].…”