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 act ivator inhibitor 1(PAI-1) activity and PAI-1 gene (4G/5G) polymorphism and diabetic retinopathy in Pima Indians with type 2 diabetes. RESEAR CH DESIGN AND METHODS - We studied 171 Pima Indians with type 2 diabet es between the ages of 30-70 years in a population-based epidemiologic al survey. Plasma PAI-1 activity was measured by a spectrophotometric assay and PAI-1 4G/5G promoter genotype by the polymerase chain reacti on (PCR) using allele-specific primers. Retinopathy was assessed by op hthalmoscopy after pupillary dilation and classified as any retinopath y 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 amo ng subjects with and without retinopathy (17.1 +/- 9.3 vs. 19.7 +/- 9. 1 arbitrary units (AU)/ml, P = 0.09). PAI-1 activity was negatively co rrelated nith duration of diabetes (rs = -0.18, P = 0.02). In a logist ic regression analysis controlled for age, sex, BMI, and duration of d iabetes, any retinopathy was significantly associated nith fasting pla sma glucose concentrations (P < 0.05), 2-h postload glucose (P = 0.02) , and HbA(1c) (P = 0.008), but not with PAI-1 activity (P = 0.48). The prevalence of retinopathy in the three genotype groups differed signi ficantly (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 contr olling for age, sex, BMI, duration of diabetes, glycated hemoglobin, a nd urine albumin-to-creatine ratio in a logistic regression analysis. The odds ratios for retinopathy in subjects with 4G/4G and 4G/5G, comp ared nith the 5G/5G genotype, were 2.0 and 3.1, respectively. CONCLUSI ONS - Although diabetic retinopathy in Pima Indians with type 2 diabet es is not associated with PAI-1 activity, subjects with the 4G/4G and 4G/5G genotype had a higher prevalence of retinopathy compared with 4G /5G PAI-1 genotype. These preliminary findings indicate that in Pima I ndians with type 2 diabetes, presence of the 4G allele of the PAI-1 ge ne was associated nith a higher risk of diabetic retinopathy.