Polymorphisms of IFN-γ (+874A/T) and IL-12 (+1188A/C) in tuberculosis patients and their household contacts in Hyderabad, India

Abstract

Several cytokine gene variants have shown to be associated with host susceptibility to infectious diseases including tuberculosis (TB). High rates of transmission were identified within household members of TB patients. In this study, we examined whether single nucleotide polymorphisms of IFN-γ +874A/T and IL-12 +1188A/C affect susceptibility to TB. Genomic DNA from patients with active disease, their household contacts HHC and healthy controls HC was genotyped for IFN-γ +874A/T and IL-12 +1188A/C SNPs by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). IFN-γ +874 AA and AT genotypes were significantly with different frequencies in patients and total HHC as compared to HC (p<0.0001). In patients IL-12 +1188 AC and CC genotypes were associated with TB (p<0.003, p<0.008). In total HHC AC, CC genotypes and both alleles (A&C) were significantly different as compared to HC (p<0.004, p<0.001, p<0.034) and the same result was obtained when HHC were stratified into related (p<0.02, p<0.001) and unrelated (p<0.009, p<0.017) individuals. Allelic frequencies, however, were significant only in related contacts (p<0.021). Generalized multifactor dimensionality reduction method (GMDR) testing revealed high risk combinations of several genotypes in IFN-γ & IL-12 genes. Our findings suggest an important role of genetic variations of IFN-γ and IL-12 for susceptibility to TB.