Association of TGF-β1 -509 C > T (rs1800469) polymorphism with bone marrow failure severity in Fanconi anemia subjects

• Published in: Molecular biology reports Vol. 52; no. 1; p. 651
• Main Authors: Chavan, Niranjan Sheshrao, George, Merin, Dhangar, Somprakash, Hadkar, Shraddha, Ghatanatti, Jagadeeshwar, Rajendran, Aruna, Nemani, Sandeep, Mudaliar, Sangeeta, Manglani, Mamta, kini, Pranoti, Vundinti, Babu Rao
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.12.2025; Springer Nature B.V
• Subjects: Adolescent; Adult; Alleles; Anemia; Animal Anatomy; Animal Biochemistry; Biomedical and Life Sciences; Bone marrow; Child; Child, Preschool; Complementation; Cytokines; DNA repair; Fanconi Anemia - genetics; Fanconi syndrome; Female; Gene expression; Gene Frequency - genetics; Gene polymorphism; Genetic Association Studies; Genetic disorders; Genetic Predisposition to Disease; Genetic variability; Genotype; Genotype & phenotype; Genotyping; Hematology; Hemoglobin; Heterozygotes; Histology; Homozygotes; Humans; Hypothesis testing; Leukocytes (neutrophilic); Life Sciences; Male; Morphology; mRNA; Original Article; Patients; Plasma; Polymorphism; Polymorphism, Single Nucleotide - genetics; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b; Transforming growth factor-b1; Young Adult; India; TGF-β1; Genotype-phenotype correlation; rs1800469; Fanconi anemia; Bone marrow failure; Gene expression
• DOI: 10.1007/s11033-025-10759-x
• ISSN: 0301-4851; 1573-4978

Background Fanconi anemia (FA) is a rare inherited genetic disorder marked by defective DNA repair mechanisms, bone marrow failure (BMF), and increased cancer susceptibility. Cytokines, specifically TGF-β are reported to be critical in FA pathophysiology, and their increased level leads to exacerbated BMF; however, the effect of genetic variability on TGF-β expression and clinical outcome remains poorly understood. This study investigates the impact of TGF-β1 -509 C > T polymorphism (rs1800469) on TGF-β expression. Methods The study was carried out on 61 confirmed diagnosed FA subjects, using chromosomal breakage studies and molecular analysis. Genotyping was performed via Sanger sequencing, and TGF-β1 quantification was carried out using ELISA and qRT-PCR. Chi-square or Fisher’s exact tests, and ANOVA (or Kruskal-Wallis tests in non-normal distributions) were performed to calculate the statistical significance. Results All 61 FA subjects showed a high frequency of chromosomal breaks and mutations in FA complementation groups. The genotyping of TGF-β1 -509 C > T polymorphism (rs1800469) revealed the following genotype frequencies: CC (41%), CT (44.2%) and TT (14.8%). The allelic frequency was C = 0.63 for the major allele and T = 0.37 for the minor allele. The TGF-β1 expression was genotype dependent. Individuals with the CC genotype showed maximum levels of TGF-β1 expression, while CT heterozygotes showed intermediate expression, and the TT homozygotes showed significantly lower levels of mRNA and protein expression. Notably, the TT genotype, associated with reduced TGF-β1 expression, correlated with improved haematological parameters, including higher haemoglobin and neutrophil count, suggesting a protective role against severe BMF. Conclusions This study suggests rs1800469 polymorphism as a critical modifier of TGF-β1 expression in FA, and suggests that the TT genotype may confer a protective advantage by reducing the severity of bone marrow failure.