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

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Abstract
Associations of the genetic polymorphisms in the promoter region and the signal peptide sequence of the transforming growth factor‐beta (TGF‐β1) 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‐β1 polymorphisms (at positions −988C/A, −800G/A, −509C/T, +869T/C (L10P), and +915G/C (R25P)) were determined by PCR‐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 (ORs) for the LL and RR genotypes were 2.89 (95% confidence interval (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 significant predictors (P = 0.002, P = 0.000003, and P = 0.007, respectively). The frequencies of genotype combinations of the −800G/A, −509C/T, L10P, and R25P TGF‐β1 polymorphisms were significantly different between the PDR and non‐PDR groups (χ2 = 37.83, df = 20, P < 10−2). The 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‐β1 gene could be regarded as a strong genetic risk factor for PDR.
Funding Information
  • Ministry of Education, Youth and Sports of the Czech Republic (CEZ J07/98:141100002)