Single nucleotide polymorphisms of the genes IL-2, IL-2RB, and JAK3 in patients with cutaneous leishmaniasis caused by Leishmania (V.) guyanensis in Manaus, Amazonas, Brazil

Abstract

Leishmaniasis is a disease caused by intracellular protozoan parasites of the genus Leishmania . In endemic areas, only a portion of exposed subjects develops cutaneous leishmaniasis (CL), suggesting that the genetic inheritance of the host plays a vital role in both resistance and susceptibility to the disease. Interleukin-2 (IL-2) is a cytokine that plays a central role in the regulation of the immune response in infection through the axis IL-2/IL-2R (receptor) complex, triggering a series of intracellular events, among which the signaling of Janus kinase/signal transducers and activators of transcription (JAK-STAT). The present study aimed at verifying the possible relationship between single nucleotide polymorphism (s) (SNP s) in the genes IL-2 , IL-2RB , and JAK3 in subjects with CL caused by Leishmania guyanensis in the city of Manaus, state of Amazonas, Brazil. 820 patients with CL and 850 healthy subjects (control group) coming from the same endemic areas as the patients were examined. The SNPs -2425G/A (rs4833248) and -330 T/G (rs2069762), located in the IL-2 gene promoter region, seem to influence the expression of the gene and the SNP +10558G/A (rs1003694) and +13295T/C (rs3212760) located in the 3rd intron of the IL-2RB gene and the 13th intron of the JAK3 gene, respectively, were studied by PCR-RFLP. Genotypes and alleles frequencies were obtained by direct counting. For the comparison between the two groups, the χ2 test with OR (odds ratio) and the 95% confidence interval (CI) were used. Similar genotypes and alleles frequencies for the different SNPs were observed in both patients with CL and healthy controls. Comparison of genotypic and allelic frequency between patients with CL and healthy subjects did not show any difference. These polymorphisms do not predict susceptibility to, or protection against the development of CL caused by L . guyanensis in the Amazonas.

TREM1 rs2234237 (Thr25Ser) Polymorphism in Patients with Cutaneous Leishmaniasis Caused by Leishmania guyanensis: A Case-Control Study in the State of Amazonas, Brazil

“…The characteristics of the study population are described elsewhere [ 28 ]. Briefly, in this study, the population was composed of 838 patients with CL and 818 HCs.…”

“…The clinical spectrum of leishmaniasis also suggests that hosts’ genetic factors are involved in the disease outcome. This points to possible host genetic contributions to the development of leishmaniasis [ 28 , 29 , 30 ]. Understanding the role of host genetics in Leishmania infections may decipher the developmental mechanism of the disease and contribute to elaborating a novel treatment for leishmaniasis, especially in the field of immunotherapy.…”

Variants of MIRNA146A rs2910164 and MIRNA499 rs3746444 are associated with the development of cutaneous leishmaniasis caused by Leishmania guyanensis and with plasma chemokine IL-8

“…The study was conducted at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD), the referral regional center for treatment of leishmaniasis. The study population and the endemic area of recruitment of the participant of the study are described elsewhere [ 30 ]. Briefly, all the participants are from the perirural areas of Manaus, the capital city of the Amazonas State where L .…”

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

“…In populations naturally exposed to Leishmania parasites, it is not yet known why some individuals develop CL and others remain healthy. This suggests that the host's genetic background plays a vital role in both resistance and susceptibility to CL 12,17,18 . Some single nucleotide polymorphisms (SNPs) of human cytokine genes have been associated with susceptibility to many diseases including infectious diseases 13,19 .…”

“…This suggests that the host's genetic background plays a vital role in both resistance and susceptibility to CL. 12,17,18 Some single nucleotide polymorphisms (SNPs) of human cytokine genes have been associated with susceptibility to many diseases including infectious diseases. 13,19 There are number of SNPs described at the genes encoding cytokines which have important roles in modulation of the immune system.…”