Searching for genetic markers of tuberculosis susceptibility

GUADALUPE INES ALVAREZ; RODRIGO HERNANDEZ DEL PINO; PACIAO VITORIO; RM MUSSELLA; DOMINGO PALMERO; GARCIA VE; PASQUINELI, V

Congreso; LXII Reunión Científica Anual de la Sociedad Argentina de Inmunología (SAI); 2014

Tuberculosis (TB) a disease caused by Mycobacterium tuberculosis (Mtb) has a large impact on public health causing 5 new million cases per year. Genetic variations of the host could determine disease susceptibility. We have studied several Single Nucleotide Polymorphisms (SNP) in candidate genes searching for new biomarkers of disease severity or susceptibility. DNA was extracted from whole blood of TB patients (PTB) and Healthy Donors (HD). +874 A/T SNP at the IFNg gene, a key cytokine in the immune response against Mtb was studied by ARMSPCR. We also studied the 262 A/T; 188 A/G (PCRRFLP) and +1343 G/T (PCR and sequencing) SNPs at SLAM (signaling lymphocytic activation molecule, an inducer of IFNg production against Mtb). For the +874 A/T SNP of IFNγ, we found an elevated frequency of the AA genotype in PTB. This SNP has been associated to TB susceptibility in other populations of the world. Our results showed a frequency of 68% for PTB vs 31% for HD for the AA genotype*** (χ2 = 41,91; p< 0,0001). The AA/GG haplotype (262 A/T and 188 A/G SLAM SNPs) was elevated in both groups of individuals (PTB=83% and HD=91% NS (χ2 = 4,92; p=0,0854)). On the other hand, the GG genotype of the +1343 G/T SLAM SNP, that has been associated previously with resistance against the measles virus, was the most frequent in both groups in our study ((PTB=70% and HD=81%) NS (χ2 = 2,93; p=0,0872)). However, by analyzing the combination of the SLAM and IFNg genotypes associated to disease resistance AT/GG or TT/GG (+874 A/T IFNγ and +1343 G/T SLAM SNPs) we found that this genotypes were overrepresented in the HD group. OR determination for all the SNPs genotypes studied showed a clear association of the AA genotype (+874 A/T SNP) of the IFNγ gene with TB (OR=6,04 IC 95% 2,631 to 13,84). The results showed that this genotype is associated with the genetic risk of developing Mtb infection.