TNF-α - 308 G/A and IFN-γ + 874 A/T gene polymorphisms in Saudi patients with cutaneous leishmaniasis

BMC Med Genet. 2020 May 13;21(1):104. doi: 10.1186/s12881-020-01043-9.

Abstract

Background: Cutaneous leishmaniasis (CL) is well linked with immunogenetic factors. This study was undertaken to test the association of TNF-α - 308 and IFN-γ + 874 gene polymorphisms with the susceptibility of Leishmania (L) species among CL patients in central region of Saudi Arabia.

Methods: This is a case-control study involved 169 Saudi subjects with different L. species and 199 healthy controls from central region of Saudi Arabia. All subjects were characterized by TNF-α - 308 G/A and IFN-γ + 874 A/T gene polymorphisms using PCR.

Results: Evaluation of genotyping and allelic frequency of TNF-α - 308 G/A in different L. species showed no significant association compared to controls (p > 0.05). Except, in cases of L. tropica that showed significantly higher TNF-α - 308 A versus G allele frequency (p = 0.0004). Evaluation of genotyping of IFN-γ + 874 (TT versus AA+AT recessive) and allelic frequency of IFN-γ + 874 (T versus A) showed significant higher in L. major and also in total CL cases as compared to healthy controls (p < 0.05). Furthermore, a strong association was observed between the susceptibility of L. major, L. tropica or total CL cases with synergistically combined high TNF-α 308/INF-γ 874 alleles.

Conclusions: This is the first report that shows the gene polymorphisms of TNF-α - 308 G/A and IFN-γ + 874 A/T in Saudi patients with different L. species infections. Data showed that the TNF-α-308 G/A gene polymorphism is not associated with the susceptibility of CL in Saudi subjects. The only correlation was found in between A versus G allelic frequency in L. tropica. Importantly, IFN-γ + 874 A/T polymorphism was found to be associated with the susceptibility of L. major and also with total CL subjects. Moreover, data from synergistically combined high TNF-α 308/INF-γ 874 alleles strongly suggest their potential role in the susceptibility of leishmania infection.

Keywords: Cutaneous leishmaniasis; Gene polymorphism; IFN-γ; L. major; L. tropica; TNF-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Interferon-gamma / genetics*
  • Leishmania
  • Leishmaniasis, Cutaneous / diagnosis
  • Leishmaniasis, Cutaneous / epidemiology
  • Leishmaniasis, Cutaneous / genetics*
  • Leishmaniasis, Cutaneous / parasitology
  • Male
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Saudi Arabia / epidemiology
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Tumor Necrosis Factor-alpha
  • Interferon-gamma