Diabetic retinopathy, promoter (4G/5G) polymorphism of PAI-1 gene, and PAI-1 activity in Pima Indians with type 2 diabetes.
OBJECTIVE
To examine the relationship between plasma plasminogen activator inhibitor 1 (PAI-1) activity and PAI-1 gene (4G/5G) polymorphism and diabetic retinopathy in Pima Indians with type 2 diabetes.


METHODS
We studied 171 Pima Indians with type 2 diabetes between the ages of 30-70 years in a population-based epidemiological survey. Plasma PAI-1 activity was measured by a spectrophotometric assay and PAI-1 4G/5G promoter genotype by the polymerase chain reaction (PCR) using allele-specific primers. Retinopathy was assessed by ophthalmoscopy after pupillary dilation and classified as any retinopathy or as nonproliferative and proliferative.


RESULTS
Retinopathy was present in 70 (41%) subjects, and 4 (2.3%) subjects had proliferative retinopathy. Plasma PAI-1 activity was not significantly different among subjects with and without retinopathy (17.1 +/- vs. 19.7 +/- 9.1 arbitrary units (AU)/ml, P = 0.09). PAI-1 activity was negatively correlated with duration of diabetes (rs = -0.18, P = 0.02). In a logistic regression analysis controlled for age, sex, BMI, and duration of diabetes, any retinopathy was significantly associated with fasting plasma glucose concentrations (P < 0.05), 2-h postload glucose (P = 0.02), and HbA1c (P = 0.008), but not with PAI-1 activity (P = 0.48). The prevalence of retinopathy in the three genotype groups differed significantly (4G/4G, 4G/5G, and 5G/5G were 44, 49, and 24%, respectively; chi 2 = 8.22, df = 2, P = 0.016) and remained significant after controlling for age, sex, BMI, duration of diabetes, glycated hemoglobin, and urine albumin-to-creatine ratio in a logistic regression analysis. The odds ratios for retinopathy in subjects with 4G/4G and 4G/5G, compared with the 5G/5G genotype, were 2.0 and 3.1, respectively.


CONCLUSIONS
Although diabetic retinopathy in Pima Indians with type 2 diabetes is not associated with PAI-1 activity, subjects with the 4G/4G and 4G/5G genotype had a higher prevalence of retinopathy compared with 5G/5G PAI-1genotype. These preliminary findings indicate that in Pima Indians with type 2 diabetes, presence of the 4G allele of the PAI-1 gene was associated with a higher risk of diabetic retinopathy.
Nagi
D K
DK
National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, USA.
McCormack
L J
LJ
Mohamed-Ali
V
V
Yudkin
J S
JS
Knowler
W C
WC
Grant
P J
PJ
D000328:Adult; D000368:Aged; D001130:Arizona / Q000453:epidemiology; D001786:Blood Glucose / Q000378:metabolism; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007198:Indians, North American; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics
D001786:Blood Glucose; D017931:DNA Primers; D017395:Plasminogen Activator Inhibitor 1; D004247:DNA