IFNG +874 T>A single nucleotide polymorphism is associated with leprosy among Brazilians

• Published in: Human genetics Vol. 128; no. 5; pp. 481 - 490
• Main Authors: Cardoso, C. C, Pereira, A. C, Brito-de-Souza, V. N, Dias-Baptista, I. M, Maniero, V. C, Venturini, J, Vilani-Moreno, F. R, de Souza, F. C, Ribeiro-Alves, M, Sarno, E. N, Pacheco, A. G, Moraes, M. O
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.11.2010; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Adult; Bacterial diseases; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Brazil - epidemiology; Case-Control Studies; Chi-Square Distribution; Classical genetics, quantitative genetics, hybrids; Cytokines; Data processing; Female; Fundamental and applied biological sciences. Psychology; gamma -Interferon; Gene Function; Genes; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Human; Human bacterial diseases; Human Genetics; Humans; Infectious diseases; Interferon-gamma - genetics; Leprosy; Leprosy - epidemiology; Leprosy - genetics; Male; Medical sciences; Metabolic Diseases; Middle Aged; Molecular Medicine; Mycobacterium; Mycobacterium leprae; Mycobacterium leprae - isolation & purification; Odds Ratio; Original Investigation; Pathogens; Peripheral blood mononuclear cells; Polymorphism; Polymorphism, Single Nucleotide; Reviews; Risk Factors; Single-nucleotide polymorphism; Tropical bacterial diseases; Tuberculosis; Tuberculosis and atypical mycobacterial infections; Virulence; South America; Brazil; America; Rio de Janeiro Brazil; Intracellular Pathogen; Leprosy; Single Nucleotide Polymorphism; PBMC Culture; Purify Protein Derivative; Infection; Skin disease; Genetic variability; Bacteriosis; Genotype; Genetics; Mycobacterial infection; Single nucleotide polymorphism
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-010-0872-x

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, a low virulence mycobacterium, and the outcome of disease is dependent on the host genetics for either susceptibility per se or severity. The IFNG gene codes for interferon-γ (IFN-γ), a cytokine that plays a key role in host defense against intracellular pathogens. Indeed, single nucleotide polymorphisms (SNPs) in IFNG have been evaluated in several genetic epidemiological studies, and the SNP +874T>A, the +874T allele, more specifically, has been associated with protection against infectious diseases, especially tuberculosis. Here, we evaluated the association of the IFNG locus with leprosy enrolling 2,125 Brazilian subjects. First, we conducted a case-control study with subjects recruited from the state of São Paulo, using the +874 T>A (rs2430561), +2109 A>G (rs1861494) and rs2069727 SNPs. Then, a second study including 1,370 individuals from Rio de Janeiro was conducted. Results of the case-control studies have shown a protective effect for +874T carriers (ORadjusted = 0.75; p = 0.005 for both studies combined), which was corroborated when these studies were compared with literature data. No association was found between the SNP +874T>A and the quantitative Mitsuda response. Nevertheless, the spontaneous IFN-γ release by peripheral blood mononuclear cells was higher among +874T carriers. The results shown here along with a previously reported meta-analysis of tuberculosis studies indicate that the SNP +874T>A plays a role in resistance to mycobacterial diseases.