TGF-β1 Gene Polymorphisms in Saudi Patients With Type 2 Diabetes With or Without Diabetic Nephropathy.

BACKGROUND

Diabetic nephropathy (DN) is a major complication of Type 2 diabetes (T2D). Transforming growth factor-beta 1 (TGF-β1), a profibrotic cytokine, promotes fibrosis in DN, and its expression is affected by gene polymorphisms. This study aimed to determine the genotypic and allelic frequencies of the TGF-β1 gene (rs1800469 and rs1800470) as well as to test whether there is an association between TGF-β1 single-nucleotide polymorphisms (SNPs) and DN development in Saudi patients with T2D.

METHODS

This case-control study involved 204 samples, including 76 controls, 81 patients with T2D without DN, and 47 patients with T2D with DN. Genotyping was performed for two TGF-β1 SNPs using real-time PCR and TaqMan. Sanger sequencing was used for validation. Chi-square testing was conducted to confirm the strength of the association between genotype and allele frequencies and the risk of developing T2D and DN.

RESULTS

The distribution of rs1800469 and rs1800470 polymorphisms was not significantly different between the participants with T2D and control participants. No significant difference was observed in the same SNPs when comparing participants with DN and control participants. The albumin level in patients with DN with the A/A genotype was the highest, whereas it was the lowest in patients with the G/G genotype of TGF-β1 rs1800470.

CONCLUSIONS

TGF-β1 rs1800470 and albuminuria are significantly associated with DN. TGF-β1 rs1800469 and rs1800470 were not significantly associated with T2D development and DN progression in Saudi patients with diabetes. Our findings suggest that continued investigation is necessary to understand the underlying mechanisms of TGF-β1 rs1800470 genotypes in DN pathogenesis.