Polymorphism R25P in the gene encoding transforming growth factor-beta (TGF-beta1) is a newly identified risk factor for proliferative diabetic retinopathy.
Associations of the genetic polymorphisms in the promoter region and the signal peptide sequence of the transforming growth factor-beta (TGF-beta1) 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-beta1 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, P(corr) < 10(-2) and P(corr) < 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-beta(1) polymorphisms were significantly different between the PDR and non-PDR groups (chi(2) = 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-beta1 gene could be regarded as a strong genetic risk factor for PDR.
Beránek
Michal
M
Department of Pathophysiology, Faculty of Medicine, Masaryk University, Lomenského námêsti 2, 662-43 Brno, Czech Republic. beranek@sci.muni.cz
Kanková
Katerina
K
Benes
Petr
P
Izakovicová-Hollá
Lydie
L
Znojil
Vladimír
V
Hájek
Dobroslav
D
Vlková
Eva
E
Vácha
Jirí
J
D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics; D003930:Diabetic Retinopathy / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000235:genetics*
D016212:Transforming Growth Factor beta; D004247:DNA