Alanine variant of the Pro12Ala polymorphism of the PPARγ gene might be associated with decreased risk of diabetic retinopathy in type 2 diabetes

ObjectiveMolecular background of diabetic retinopathy (DR) remains unknown. An interesting group of candidate genes encode proteins involved in insulin resistance.AimTo search for association between the PPARγ, calpain 10, PTPN1 genes and DR in type 2 diabetes mellitus (T2DM).MethodsWe examined 238 T2DM subjects without DR (NDR) and 121 with DR (mean diabetes duration: 9.1 ± 6.8 and 15.1 ± 7.7, respectively). The subjects were genotyped for four markers: Pro12Ala of PPARγ, SNP43 of calpain 10, rs3787345 and rs754118 of PTPN1. The distributions of the genotypes were compared using the χ2-test and Fisher exact test.ResultsThe alleles and genotypes were not associated with DR in non-stratified analysis. To investigate the impact of T2DM duration, we performed analysis that excluded short duration NDR subjects and long-duration DR subjects. It allowed obtaining groups with similar T2DM duration but different DR status (DR: 88 individuals, 11.4 ± 5.3 years; NDR: 136 individuals, 13.2 years ± 6.2, respectively). This analysis suggested that the alanine variant of Pro12Ala might be associated with decreased risk of DR (p = 0.026 for alleles, p = 0.038 and p = 0.014 for genotypes in additive and dominant models, respectively). In multivariable logistic regression that included non-genetic parameters, Pro12Ala was not an independent risk factor (p = 0.28). Further analysis showed, however, that Pro12Ala remained significant when urea level was excluded from the model.ConclusionThe alanine variant of the Pro12Ala polymorphism of PPARγ might be associated with decreased risk of DR in T2DM. This effect may be indirect, at least in part, due to diabetic kidney disease.