The Genetic Association of SP-A and SP-D Polymorphisms with Tuberculosis and Latent TB in the Pakistani Population
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Abstract
Background: Tuberculosis (TB) remains a major global health concern, posing a substantial burden in Pakistan. Genetic factors play a pivotal role in individual susceptibility to TB. Surfactant protein A and surfactant protein D are essential components of the innate immune system, contributing to pulmonary host defense against Mycobacterium tuberculosis (MTB). Aim This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in the SP-A1gene at rs1059047 (+1101 C/T) and the SP-D gene at rs3088308 (911 T/A) and TB susceptibility in the Pakistani population. Method A case-control study was conducted, comprising 350 individuals, including 150 healthy controls, 100 TB patients, and 100 TB contacts. Genotyping was performed using tetra ARMS-PCR. Functional effects of the SNPs were evaluated through in-silico prediction tools including SIFT, PolyPhen-2, REVEL, AlphaMissense, and CADD using the SNPnexus annotation platform. GraphPad Prism v.10 was used for statistical analysis. Results Our results revealed no significant association between the SP-A1 gene polymorphism at rs1059047 (+1101 C/T) and SP-D gene polymorphism at rs3088308 (911 T/A) and TB susceptibility in the Pakistani population (p>0.5). Interestingly, concerning the rs3088308 polymorphism in the SP-D gene, a comparison between healthy controls and TB contacts indicated that the homozygous TT genotype was significantly associated with protection against LTBI (73.53% vs. 82.35%; p=0.00, OR=0.19, 95% CI=0.08-0.51. In-silico analysis predicted rs1059047 to be tolerated by SIFT (0.750) and likely benign by AlphaMissense (0.0588–0.0596) and CADD (0.034), while rs3088308 was also predicted as tolerated/benign by SIFT (0.100), PolyPhen-2 (0.118), REVEL (0.050), and AlphaMissense (0.200000), with CADD (14.540) suggesting a low-confidence deleterious effect, overall indicating that these variants are unlikely to significantly disrupt the functional integrity of SP-A and SP-D proteins.
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Abstract
Background: Tuberculosis (TB) remains a major global health concern, posing a substantial burden in Pakistan. Genetic factors play a pivotal role in individual susceptibility to TB. Surfactant protein A and surfactant protein D are essential components of the innate immune system, contributing to pulmonary host defense against Mycobacterium tuberculosis (MTB).
Aim: This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in the SP-A1gene at rs1059047 (+1101 C/T) and the SP-D gene at rs3088308 (911 T/A) and TB susceptibility in the Pakistani population.
Method
A case-control study was conducted, comprising 350 individuals, including 150 healthy controls, 100 TB patients, and 100 TB contacts. Genotyping was performed using tetra ARMS-PCR. Functional effects of the SNPs were evaluated through in-silico prediction tools including SIFT, PolyPhen-2, REVEL, AlphaMissense, and CADD using the SNPnexus annotation platform. GraphPad Prism v.10 was used for statistical analysis.
Results
Our results revealed no significant association between the SP-A1 gene polymorphism at rs1059047 (+1101 C/T) and SP-D gene polymorphism at rs3088308 (911 T/A) and TB susceptibility in the Pakistani population (p>0.5). Interestingly, concerning the rs3088308 polymorphism in the SP-D gene, a comparison between healthy controls and TB contacts indicated that the homozygous TT genotype was significantly associated with protection against LTBI (73.53% vs. 82.35%; p=0.00, OR=0.19, 95% CI=0.08-0.51. In-silico analysis predicted rs1059047 to be tolerated by SIFT (0.750) and likely benign by AlphaMissense (0.0588–0.0596) and CADD (0.034), while rs3088308 was also predicted as tolerated/benign by SIFT (0.100), PolyPhen-2 (0.118), REVEL (0.050), and AlphaMissense (0.200000), with CADD (14.540) suggesting a low-confidence deleterious effect, overall indicating that these variants are unlikely to significantly disrupt the functional integrity of SP-A and SP-D proteins.
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