02702nas a2200445   4500000000100000008004100001260001300042653001000055653001100065653002500076653002800101653001100129653003800140653001100178653002100189653001200210653000900222653001600231653002500247653001500272653003600287653001700323100001600340700001600356700002300372700002200395700001600417700001600433700002200449700001400471700002000485700001400505700001600519700001500535245009400550300001100644490000800655520157900663022001402242       2010                            d  c2010 Nov10aAdult10aBrazil10aCase-Control Studies10aChi-Square Distribution10aFemale10aGenetic Predisposition to Disease10aHumans10aInterferon-gamma10aleprosy10aMale10aMiddle Aged10aMycobacterium leprae10aOdds Ratio10aPolymorphism, Single Nucleotide10aRisk Factors1 aCardoso C C1 aPEREIRA A C1 aBrito-de-Souza V N1 aDias-Baptista I M1 aManiero V C1 aVenturini J1 aVilani-Moreno F R1 aSouza F C1 aRibeiro-Alves M1 aSarno E N1 aPacheco A G1 aMoraes M O00aIFNG +874 T>A single nucleotide polymorphism is associated with leprosy among Brazilians.  a481-900 v1283 a<p>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 (OR(adjusted) = 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.</p>  a1432-1203