Polymorphism R25P in the gene encoding transforming growth factor‐beta (TGF‐β1) is a newly identified risk factor for proliferative diabetic retinopathy

Association of the genetic polymorphisms in the promoter region and the signal peptide sequence of the transforming growth factor-beta (TGF-s1) gene with proliferative diabetic retinopathy (PDR) in patients with non-insulin dependent diabetes mellitus (NIDDM) were studied. A total of 245 Caucasian subjects comprised the two groups: NIDDM patients with PDR (n=73) and NIDDM patients without PDR (n=172). Allele frequencies of common TGF-s1 polymorphisms (at positions -988C/A, -800G/A, -509C/T, +869T/C (L10P) and +915G/C (R25P)) were determined by polymerase chain reaction based methodology. All polymorphisms were in strong linkage disequilibrium (P<10-2). Significantly higher frequencies of both the L allele and the R allele of the signal sequence polymorphisms in PDR subjects were found (after a correction for multiple comparisons Pcorr<10-2 and Pcorr<10-4, respectively). Calculated odds ratios for the LL and RR genotypes were 2.89 (95% CI, 1.6-5.1) and 19.73 (95% CI, 2.6-146.8), respectively. No significant differences between groups were found for the -800G/A and - 509C/T polymorphisms. The - 988A allele was not represented in our sample. Multiple logistic regression identified age, diabetes duration and R25P polymorphism as a significant predictors (P=0.002, P=0.000003, P= 0.007, respectively). The frequencies of genotype combinations of the -800G/A, -509C/T, L10P and R25P TGF-s1 polymorphisms were significantly different between the PDR and non-PDR groups (?2=37.83, df=20, P<10-2). Frequency of haplotype consisting of majority alleles was found significantly associated with PDR (P<0.03). The presented data indicate that the R25P polymorphisms in the TGF-s1 gene could be regarded as a strong genetic risk factor for PDR.