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Haplotype Structures and Protein Levels of TGFB1 in HPV Infection and Cervical Lesion: A Case-Control Study
Kleber Paiva Trugilo1, Guilherme Cesar Martelossi Cebinelli1, Érica Romão Pereira1,2
1Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina 86057-970, PR, Brazil.
Cells
|January 8, 2023
Summary
Specific transforming growth factor beta 1 (TGFB1) gene variants influence susceptibility to human papillomavirus (HPV) infection and cervical lesion development. These TGFB1 variants also impact TGFB1 levels in cervical tissues and plasma.
Area of Science:
- Genetics
- Oncology
- Immunology
Background:
- Cervical cancer is a significant global health concern, primarily caused by persistent human papillomavirus (HPV) infection.
- Transforming growth factor beta 1 (TGFB1) plays a crucial role in immune regulation and tissue remodeling, potentially influencing HPV infection and disease progression.
Purpose of the Study:
- To investigate the association between specific single nucleotide polymorphisms (SNPs) and haplotypes in the TGFB1 gene and HPV infection susceptibility.
- To determine the impact of these TGFB1 variants on the development of cervical lesions.
- To analyze the effect of TGFB1 variants on TGFB1 protein levels in cervical tissue and plasma.
Main Methods:
- Genotyping of four TGFB1 variants (c.-1638G>A, c.-1347C>T, c.29C>T, and c.74G>C) using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).
- Haplotype inference for 190 HPV-uninfected and 161 HPV-infected women.
- Quantification of TGFB1 levels in plasma and cervical samples via immunofluorimetric assay.
- Statistical analysis using logistic regression, adjusted for potential confounders.
Main Results:
- Specific TGFB1 genotypes (-1347TT, -1347CT+TT, 29CT, 29CC, 29CT+CC) were associated with increased HPV infection risk.
- The TGFB1 haplotype *4 (GCTG) was linked to decreased HPV susceptibility, while haplotype *3 (GTCG) was associated with increased susceptibility.
- Elevated TGFB1 plasma and cervical levels were observed in HPV-infected individuals, particularly in those with low-grade lesions.
- Certain TGFB1 haplotypes (*3/Other, *3/Other+*3/*3) in infected patients correlated with lower plasma TGFB1 levels.
Conclusions:
- Genetic variations in the TGFB1 gene are implicated in HPV infection susceptibility and the pathogenesis of HPV-related cervical lesions.
- TGFB1 levels are altered in HPV infection and may be modulated by specific TGFB1 genotypes and haplotypes.
- These findings contribute to understanding the complex interplay between TGFB1, HPV, and cervical disease, potentially informing future diagnostic or therapeutic strategies.
