Effect of 4G/5G PAI-1 polymorphism on the response of PAI-1 activity to vitamin E supplementation in Type 2 diabetic patients.
Plasminogen activator inhibitor type 1 (PAI-1) is an independent cardiovascular risk factor and increases in patients with Type 2 diabetes mellitus. The 4G/5G polymorphism of PAI-1 has been reported to be involved in the incidence of cardiovascular disease by regulation of PAI-1 levels, but this relation is still under debate. The aim of the study was to test the effect of 4G/5G polymorphism on the lowering of PAI-1 levels in Type 2 diabetic patients during vitamin E supplementation. Ninety-three Type 2 diabetic subjects (age +/- SD, 62.1 +/- 6.1 yr) were enrolled and treated with vitamin E (500 IU/die) for 10 weeks. We determined the 4G/5G polymorphism and PAI-1 activity at baseline, during (5th and 10th week) and after (30th week) vitamin E supplementation. No significant differences were found in PAI-1 and its determinants among the three genotypic groups at baseline. Decrements were detected in the whole group in PAI-1 at the 5th and the 10th week from baseline followed by an increase at the 30th week (p<0.001). Patients with 4G/4G and 4G/5G genotypes showed a different trend with respect to those with 5G/5G in PAI-1. In particular, there was a decrease in 4G/4G and 4G/5G PAI-1 levels from the 10th week, while a decrease in 5G/5G PAI-1 was observed from the 5th week (p<0.01). The delayed decrease, found in patients with at least one 4G allele with respect to those with 5G/5G genotype, demonstrates that 4G/5G polymorphism mainly influences the rate of decrease of PAI-1 after supplementation with vitamin E in Type 2 diabetic subjects.
Testa
R
R
INRCA, Italian National Research Center on Aging, Ancona, Italy. r.testa@inrca.it
Bonfigli
A R
AR
Sirolla
C
C
Boemi
M
M
Manfrini
S
S
Mari
D
D
Testa
I
I
Sacchi
E
E
Franceschi
C
C
D000975:Antioxidants / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D019587:Dietary Supplements; D005260:Female; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D017395:Plasminogen Activator Inhibitor 1; D014810:Vitamin E