Smoking and the genetics of signal transduction: an association study on retinopathy in type 1 diabetes.
BACKGROUND
Recent studies suggest a complex association between smoking and retinopathy that probably depends on the interaction between many variables. We have reported an association between ACP1 phenotype and retinopathy in type 1 diabetes. Additionally, the deleterious effects of smoking on intrauterine growth are dependent on ACP1, a low-molecular-weight tyrosine phosphatase that modifies signal transduction. We examine here the interaction between smoking and ACP1 as a mediator of susceptibility to diabetic retinopathy in a sample of puerperae with type 1 diabetes.


METHODS
Seventy-eight women who had just delivered live infants were studied. ACP1 phenotype was determined by starch gel electrophoresis. Three-way contingency tables were analyzed.


RESULTS
There is a significant epistatic interaction between smoking and ACP1 phenotype concerning their effects on retinopathy. In subjects with low ACP1 activity, frequency of retinopathy was slightly higher in smokers than in nonsmokers. However, in subjects with medium-high ACP1 activity, frequency of retinopathy was significantly lower in smokers than in nonsmokers. A logistic regression analysis using retinopathy as the dependent variable revealed that smoking, ACP1, and ACP1 by smoking interaction, as well as the interaction between smoking and age of the women, are the most robust predictors of retinopathy.


CONCLUSIONS
The effect of smoking on retinopathy in women with type 1 diabetes depends on many variables, which supports the hypothesis of complex interactions between smoking and other variables in the pathogenesis of this disease. Variability of genetic factors involved in signal transduction may affect endothelium proliferation through the regulation of growth factors and through regulation of glycemic levels. Because cigarette smoke influences signal transduction, its impact on diabetic retinopathy may be mediated by ACP1.
Magrini
A
A
Section of Occupational Health Medicine, Department of Biopathology and Imaging Diagnostics, University of Rome Tor Vergata, Rome, Italy.
Bottini
N
N
Nicotra
M
M
Cosmi
E
E
Bottini
E
E
Bergamaschi
A
A
D000328:Adult; D000367:Age Factors; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000503:physiopathology*; D004843:Epistasis, Genetic; D005260:Female; D038321:Glycemic Index; D006801:Humans; D007231:Infant, Newborn; D007527:Isoenzymes; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000503:physiopathology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D012044:Regression Analysis; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D012907:Smoking; D013223:Statistics as Topic
D001786:Blood Glucose; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; C490429:ACP1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases