Alanine variant of the Pro12Ala polymorphism of the PPARgamma gene might be associated with decreased risk of diabetic retinopathy in type 2 diabetes.
OBJECTIVE
Molecular background of diabetic retinopathy (DR) remains unknown. An interesting group of candidate genes encode proteins involved in insulin resistance.


OBJECTIVE
To search for association between the PPARgamma, calpain 10, PTPN1 genes and DR in type 2 diabetes mellitus (T2DM).


METHODS
We 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 PPARgamma, SNP43 of calpain 10, rs3787345 and rs754118 of PTPN1. The distributions of the genotypes were compared using the chi(2)-test and Fisher exact test.


RESULTS
The 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.


CONCLUSIONS
The alanine variant of the Pro12Ala polymorphism of PPARgamma might be associated with decreased risk of DR in T2DM. This effect may be indirect, at least in part, due to diabetic kidney disease.
Malecki
Maciej T
MT
Department of Metabolic Diseases, Jagiellonian University Medical College, 15 Kopernika Street, 31-501 Krakow, Poland. malecki_malecki@yahoo.com
Cyganek
Katarzyna
K
Mirkiewicz-Sieradzka
Barbara
B
Wolkow
Pawel P
PP
Wanic
Krzysztof
K
Skupien
Jan
J
Solnica
Bogdan
B
Sieradzki
Jacek
J
D000368:Aged; D000409:Alanine / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
D047495:PPAR gamma; D000409:Alanine