Transforming growth factor beta 1 (TGFβ1) polymorphisms and unexplained infertility: A genetic association study

Area of Science:

• Genetics
• Reproductive Biology
• Immunology

Background:

• Increasing prevalence of infertility, with 10-30% classified as unexplained infertility (UI).
• Transforming growth factor-beta 1 (TGF-β1) is a crucial cytokine for implantation and pregnancy.
• The role of TGF-β1 gene polymorphisms in UI susceptibility requires further investigation.

Purpose of the Study:

• To investigate the association between TGF-β1 gene polymorphisms (rs1800470 and rs1800471) and unexplained infertility in an Iranian population.
• To analyze the in-silico effects of these polymorphisms on TGF-β1 mRNA and protein structure and function.

Main Methods:

• Genotyping of 250 UI patients and 484 healthy controls using PCR and automated sequencing for TGF-β1 polymorphisms rs1800470 (C29T) and rs1800471 (G74C).
• In-silico analysis to predict the impact of polymorphisms on TGF-β1 mRNA secondary structure, protein function, and mRNA half-life.

Main Results:

• Statistically significant differences in allele, genotype, and haplotype frequencies of TGF-β1 polymorphisms between UI patients and controls.
• The CC genotype of rs1800470 was associated with increased UI risk in males; the C allele of rs1800471 was linked to increased UI risk in females.
• Haplotypes TG and CG showed significant differences between UI patients and healthy subjects. Polymorphisms altered TGF-β1 mRNA secondary structure and potentially reduced its expression.

Conclusions:

• Functional polymorphisms in the TGF-β1 gene are associated with unexplained infertility susceptibility in the Iranian population.
• Specific TGF-β1 genotypes and alleles contribute to increased UI risk in males and females, respectively.
• In-silico findings suggest that TGF-β1 polymorphisms may reduce mRNA half-life, impacting TGF-β1 expression and contributing to infertility.