Single Nucleotide Polymorphisms in IL17A and IL6 Are Associated with Decreased Risk for Pulmonary Tuberculosis in Southern Brazilian Population

Abstract

In Mycobacterium tuberculosis (MTB) infection, the complex interaction of host immune system and the mycobacteria is associated with levels of cytokines production that play a major role in determining the outcome of the disease. Several single-nucleotide polymorphisms (SNPs) in cytokine genes have been associated with tuberculosis (TB) outcome. The aim of this study was to evaluate the association between previously reported SNPs IL2–330 T>G (rs2069762); IL4–590 C>T (rs2243250); IL6–174 G>C (rs1800795); IL10–592 A>C (rs1800872); IL10–1082 G>A (rs1800896); IL17A -692 C>T (rs8193036); IL17A -197 G>A (rs2275913); TNF -238 G>A (rs361525); TNF -308 G>A (rs1800629) and IFNG +874 T>A (rs2430561) and pulmonary TB (PTB) susceptibility. We conducted a case-control study in individuals from Southern Brazil who were recruited between February 2012 and October 2013 in a high incidence TB city. We performed a multiplex genotyping assay in 191 patients with PTB and 175 healthy subjects. Our results suggest a decreased risk for PTB development associated with the IL17A -197A allele (OR = 0.29; p = 0.04), AA genotype (OR = 0.12; p = 0.04) and A carrier (AGAA) (OR = 0.29; p = 0.004) and IL6 -174C carrier (CC/CG) (OR = 0.46; p = 0.04). We could not properly analyze IL17A -692 C>T (rs8193036) and IFNG +874T>A due to genotypic inconsistencies and found no evidence of association for the IL2, IL4, IL10 and TNF polymorphisms and PTB. In conclusion, our results show a protective effect of IL17 and IL6 polymorphisms on PTB outcome in Southern Brazilian population.

The IL-17A rs2275913 single nucleotide polymorphism is associated with protection to tuberculosis but related to higher disease severity in Argentina

“…However, the TB population studied did not show HW equilibrium. In contrast, both in a population from North Spain9 and another one at the South of Brazil10, populations in which the HW equilibrium condition was fulfilled, the A allele and the AA genotype displayed the lowest frequencies in the TB population, in agreement with our present findings. Thus, our data are consistent with previous reports, further supporting the idea of a higher resistance to tuberculosis disease in AA individuals and highlighting the important function of IL-17A in immunity against Mtb .…”

“…In order to find an association with resistance/susceptibility to tuberculosis, several studies investigated the rs2275913 SNP in ethnically different populations910134142. In a Croatian41 and a Chinese42 populations, no association between the SNP and tuberculosis were detected.…”

“…It has been reported that allelic variants of the rs2275913 SNP differentially bind the transcription factor NFAT, leading to differences in IL-17A secretion30. Three previous reports demonstrated an association between the rs2275913 SNP and tuberculosis in populations from Spain, Brazil and China91013. Therefore, the aim of this study was to investigate the potential association of the IL-17A rs2275913 SNP and tuberculosis in Argentina.…”

“…Particularly in tuberculosis, several SNPs have been reported as possible causes of disease resistance/susceptibility. Among them, there were described variations in cytokine genes such as IFN-γ, TNF-α, IL-1, IL-6, IL-10, IL-12 and IL-178910111213. However, only one study in the Argentinean population has reported the association between an IL-12 SNP and tuberculosis14.…”

Interleukin-17F and interleukin-6 gene polymorphisms in Asian Indian patients with Takayasu arteritis

“…However, in our previous work (20) on circulatory serum cytokine levels in 30 TA patients, we did observe a trend towards higher IL-6 levels in patients with active disease (20.5pg/ml, range:1.6-72pg/ml) as compared to those with stable disease (7.2 pg/ml, range:1-68 pg/ml), p=0.053 (20). Association of GG genotype of this SNP (rs1800795 in IL-6 gene) with TA in Turkish population (10) could be due to higher IL-6 levels associated with G allele as GC substitution at position -174 upstream of transcription site of IL-6 gene results in decrease in serum IL-6 levels.…”