SLC11A1 (rs3731865) polymorphism and susceptibility to visceral leishmaniasis in HIV-coinfected patients from Northeastern Brazil

Parasitol Res. 2020 Feb;119(2):491-499. doi: 10.1007/s00436-019-06596-0. Epub 2020 Jan 6.

Abstract

Following the emergence of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), the number of visceral leishmaniasis-HIV (VL-HIV) coinfections has increased worldwide, mainly in Brazil. The development of clinical forms of VL can be influenced by nutritional status, age, and host genetic factors, which are important variables determining susceptibility to disease. There are no studies with a candidate gene approach assayed directly in the VL-HIV-coinfected population. Herein, we determined and analyzed the associations of SLC11A1, LECT2, CCL1, CCL16, and IL4 genetic polymorphisms with susceptibility to VL-HIV coinfection in Northeastern Brazil. We analyzed 309 DNA samples extracted from the peripheral blood of HIV patients, and clinical and hematological data were collected from medical records. The diagnosis of VL was confirmed in 110 out of 309 patients; genotyping was carried out by TaqMan assays afterwards. Our results confirmed the association between the SLC11A1 polymorphism (rs3731865) and VL-HIV coinfection (p = 0.0206, OR 1.8126, 95% CI 1.1050-2.9727). In addition, the SLC11A1 genotype GG (p = 0.0050, OR 3.0395, 95% CI 1.4065-6.5789) and CD4+ T lymphocyte count (p = 0.0030, OR 0.9980, 95% CI 0.9970-0.9990) were associated with VL-HIV coinfection in a multivariate model. The polymorphism of the SLC11A1 gene (rs3731865) was associated with VL-HIV coinfection, suggesting a possible genetic mechanism involved in the susceptibility to VL in HIV patients. This finding can suggest new therapeutic targets and genetic markers for the VL-HIV-coinfected population.

Keywords: HIV; Polymorphisms; Susceptibility; Visceral leishmaniasis.

MeSH terms

  • Acquired Immunodeficiency Syndrome / epidemiology*
  • Adult
  • Brazil / epidemiology
  • CD4-Positive T-Lymphocytes / immunology
  • Cation Transport Proteins / genetics*
  • Chemokine CCL1 / genetics
  • Chemokines, CC / genetics
  • Coinfection / epidemiology
  • Coinfection / genetics
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Interleukin-4 / genetics
  • Leishmaniasis, Visceral / epidemiology*
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics

Substances

  • CCL1 protein, human
  • CCL16 protein, human
  • Cation Transport Proteins
  • Chemokine CCL1
  • Chemokines, CC
  • IL4 protein, human
  • Intercellular Signaling Peptides and Proteins
  • LECT2 protein, human
  • natural resistance-associated macrophage protein 1
  • Interleukin-4