Association Between Functional Nucleotide Polymorphisms Up-regulating Transforming Growth Factor β1 Expression and...

Area of Science:

• Immunology
• Genetics
• Infectious Diseases

Background:

• Transforming growth factor-beta 1 (TGF-β1) is known to have an immunosuppressive role in clinical tuberculosis.
• The specific contribution of TGF-β1 gene polymorphisms to tuberculosis susceptibility in humans has not been fully determined.

Purpose of the Study:

• To investigate the association between single-nucleotide polymorphisms (SNPs) in the TGF-β1 gene and susceptibility to tuberculosis.
• To explore the role of these SNPs in tuberculosis severity and immune response modulation.

Main Methods:

• Case-control study design involving a discovery cohort (1533 cases, 1445 controls) and a validation cohort (832 cases, 1084 controls).
• Analysis of single-nucleotide polymorphisms (SNPs) in the TGF-β1 gene, including linkage disequilibrium analysis for promoter region SNPs (rs2317130 and rs4803457).
• Measurement of TGF-β1 and interleukin 17A levels; investigation of the effect of the rs2317130 C allele on TGF-β1 promoter activity and nuclear extract binding.

Main Results:

• SNPs in the TGF-β1 gene were significantly associated with increased susceptibility to tuberculosis in both cohorts.
• The SNP rs2317130 was linked to increased tuberculosis severity.
• The rs2317130 CC genotype correlated with higher levels of TGF-β1 and interleukin 17A.
• The rs2317130 C allele demonstrated an impact on TGF-β1 promoter activity by altering nuclear extract binding.

Conclusions:

• TGF-β1 gene polymorphisms contribute to human susceptibility and severity of tuberculosis.
• The rs2317130 SNP in the TGF-β1 promoter region plays a role in regulating immune responses during Mycobacterium tuberculosis infection.
• These findings elucidate the pathogenic role of TGF-β1 in tuberculosis and highlight the functional significance of its promoter SNPs.