02453nas a2200529   4500000000100000008004100001260004900042653001000091653001100101653002500112653000800137653001100145653002200156653001300178653001100191653001200202653000900214653002500223653003000248653003600278653003200314653001600346100001400362700001500376700002100391700001300412700002000425700001200445700001500457700001900472700001700491700001200508700001500520700001400535700001400549700001800563700001200581700001300593700001200606700001400618700001300632245016400645300001200809490000800821520108000829022001401909       2011                            d  c2011 Oct 15bOxford University PressaOxford10aAdult10aBrazil10aCase-Control Studies10aDNA10aFemale10aGenetic Variation10agenotype10aHumans10aleprosy10aMale10aMycobacterium leprae10apolymerase chain reaction10aPolymorphism, Single Nucleotide10aTumor Necrosis Factor-alpha10aYoung Adult1 aCardoso C1 aPereira AC1 aBrito-de-Souza V1 aDuraes S1 aRibeiro-Alves M1 aNery JA1 aFrancio Â1 aVanderborght P1 aParelli FP C1 aAlter A1 aSalgado JL1 aSampaio E1 aSantos AR1 aOliveira MLWD1 aSarno E1 aSchurr E1 aMira MT1 aPacheco A1 aMoraes M00aTNF -308G>A single nucleotide polymorphism is associated with leprosy among Brazilians: a genetic epidemiology assessment, meta-analysis, and functional study.  a1256-630 v2043 a<p>Leprosy is an infectious disease caused by Mycobacterium leprae. Tumor necrosis factor (TNF) plays a key role in the host response. Some association studies have implicated the single nucleotide polymorphism TNF -308G>A in leprosy susceptibility, but these results are still controversial. We first conducted 4 association studies (2639 individuals) that showed a protective effect of the -308A allele (odds ratio [OR] = 0.77; P = .005). Next, results of a meta-analysis reinforced this association after inclusion of our new data (OR = 0.74; P = .04). Furthermore, a subgroup analysis including only Brazilian studies suggested that the association is specific to this population (OR = 0.63; P = .005). Finally, functional analyses using whole blood cultures showed that patients carrying the -308A allele produced higher TNF levels after lipopolysaccharide (LPS) (6 hours) and M. leprae (3 hours) stimulation. These results reinforce the association between TNF and leprosy and suggest the -308A allele as a marker of disease resistance, especially among Brazilians.</p>  a1537-6613