SP-D TT variant may protect contacts from latent tuberculosis in Pakistan

Tuberculosis (TB) remains a major health challenge, and researchers are still trying to understand why some people become sick while others do not. The burden of TB in Pakistan makes this question especially important there. Genetic differences between people can shape how well the immune system responds to the bacterium Mycobacterium tuberculosis (MTB), which causes TB. Surfactant protein A and surfactant protein D are part of the lung’s innate immune system and help defend the airways against pathogens such as MTB. To explore whether small genetic changes influence TB risk in a Pakistani population, a team led by corresponding author Sidra Younis examined two single nucleotide polymorphisms (SNPs): one in the SP-A1 gene at rs1059047 (+1101 C/T) and one in the SP-D gene at rs3088308 (911 T/A). The study used a case-control design including 350 people: 150 healthy controls, 100 people diagnosed with TB, and 100 TB contacts (people exposed to TB). By comparing these groups, the researchers sought to see whether specific versions of these genes were linked to active disease or to latent infection.

The study genotyped participants using tetra ARMS-PCR and carried out statistical analysis with GraphPad Prism v.10. The investigators tested the SP-A1 gene polymorphism at rs1059047 (+1101 C/T) and the SP-D gene polymorphism at rs3088308 (911 T/A) across the three groups: healthy controls, TB patients, and TB contacts. Overall, the analysis did not find a significant association between either the SP-A1 rs1059047 variant or the SP-D rs3088308 variant and susceptibility to active TB in this Pakistani sample (p>0.5). However, a more focused comparison between healthy controls and TB contacts revealed a notable result for the SP-D rs3088308 polymorphism: the homozygous TT genotype was significantly associated with protection against latent TB infection (LTBI). The reported frequencies were 73.53% in one group versus 82.35% in the other, with p=0.00, OR=0.19 and 95% CI=0.08-0.51. In plain terms, people with the TT genotype at rs3088308 were less likely to have latent infection among contacts in this study.

These findings offer two clear messages. First, in this Pakistani study population, the two tested SNPs—SP-A1 rs1059047 (+1101 C/T) and SP-D rs3088308 (911 T/A)—do not appear to be major drivers of susceptibility to active TB, since no significant association with disease was detected. Second, the association of the SP-D rs3088308 TT genotype with lower rates of latent TB among contacts suggests a possible protective effect against acquiring or maintaining LTBI after exposure. That pattern could point to a role for surfactant protein D in determining who develops latent infection following exposure to MTB. Importantly, these results come from a single study of 350 people and apply to the Pakistani population sampled; they should be treated as preliminary. Further research, including larger and diverse populations and replication of the rs3088308 finding, would be needed before this genetic information could be used for screening, risk assessment, or public health planning.