It was recently shown that the transcription factor T-bet is crucial for adequate innate and acquired immune responses to genital herpes simplex virus type 2 (HSV-2) infection in mice. To test the possible genetic influence of variations in the TBX21 gene encoding T-bet on susceptibility to infection, this study evaluated the frequencies of five different single-nucleotide polymorphisms (SNPs) in the human TBX21 gene in 159 HSV-2-infected individuals and compared them with those in 186 healthy HSV-2-seronegative controls. The data showed that one variation (rs17244587) in the 3'-untranslated region of TBX21 was strongly associated with the incidence of genital HSV-2 infection. The frequency of the A allele at this position was 0.19 in the group of HSV-2-infected individuals compared with 0.05 in the group of uninfected controls (P=9.3x10(-8)). Furthermore, a homozygous AA genotype was found only among HSV-2-infected individuals and not in seronegative controls. These results indicate that the host genetic background may affect susceptibility to HSV-2 infection in humans, with TBX21 as a strong candidate gene.
