TGFB1 and IL8 gene polymorphisms and susceptibility to visceral leishmaniasis

• Published in: Infection, genetics and evolution Vol. 11; no. 5; pp. 912 - 916
• Main Authors: Frade, Amanda Farage, Oliveira, Lea Campos de, Costa, Dorcas Lamounier, Costa, Carlos Henrique Nery, Aquino, Dorlene, Van Weyenbergh, Johan, Barral-Netto, Manoel, Barral, Aldina, Kalil, Jorge, Goldberg, Anna Carla
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01-07-2011; Elsevier
• Subjects: Adolescent; Adult; Aged; Alleles; Biological and medical sciences; Child; Child, Preschool; Cytokines; delayed hypersensitivity; disease severity; Disease susceptibility; Epidemiology. Vaccinations; Female; Gene polymorphisms; General aspects; Genetic Predisposition to Disease; Genotype; hemorrhage; Human protozoal diseases; Humans; Infant; Infectious diseases; interleukin-8; Interleukin-8 - genetics; Leishmania; Leishmaniasis, Visceral - genetics; Leshmaniasis; Male; Medical sciences; Middle Aged; natural history; parasites; Parasitic diseases; patients; polymerase chain reaction; Protozoal diseases; restriction fragment length polymorphism; risk; Transforming Growth Factor beta1 - genetics; Visceral leishmaniasis; Gene polymorphisms; Disease susceptibility; Cytokines; Visceral leishmaniasis; Infection; Protozoal disease; Cytokine; Molecular epidemiology; Kala azar; Leishmaniasis; Parasitosis; Polymorphism
• ISSN: 1567-1348; 1567-7257
• DOI: 10.1016/j.meegid.2011.02.014

Visceral leishmaniasis (VL) or Kala-azar is a serious protozoan infectious disease caused by an obligate intracellular parasite. Cytokines have a major role in determining progression and severity of clinical manifestations in VL. We investigated polymorphisms in the
TGFB1and
IL8 genes, which are cytokines known to have a role in onset and severity of the disease. Polymorphisms at
TGFB1 −509 C/T and +869 T/C, and
IL8 −251 A/T were analyzed by a PCR-RFLP technique, in 198 patients with VL, 98 individuals with asymptomatic infection positive for a delayed-type hypersensitivity test (DTH+) and in 101 individuals with no evidence of infection (DTH−). The presence of the T allele in position −509 of the
TGFB1 gene conferred a two-fold risk to develop infection both when including those with clinical symptoms (DTH+ and VL, grouped) or when considering DTH+ only, respectively
p
=
0.007, OR
=
1.9 [1.19–3.02] and
p
=
0.012, OR
=
2.01 [1.17–3.79], when compared with DTH− individuals. In addition, occurrence of hemorrhage was associated with
TGFB1 −509 T allele. We suggest that the −509 T allele of the
TGFB1 gene, a cytokine with a biologically relevant role in the natural history of the disease, may contribute to overall susceptibility to infection by
Leishmania and to severity of the clinical disease.