The -675 4G/5G polymorphism at the Plasminogen Activator Inhibitor 1 (PAI-1) gene modulates plasma Plasminogen Activator Inhibitor 1 concentrations in response to dietary fat consumption.
The objective of the study was to determine whether Plasminogen Activator Inhibitor Type 1 (PAI-1) -675 4G/5G polymorphism is associated with the response of functional plasma PAI-1 concentrations to changes in the amount and quality of dietary fat in healthy subjects. PAI-1 is the major inhibitor of fibrinolysis, and a lower level of fibrinolytic activity could be implicated in an increased risk of IHD. Fifty-nine healthy Spanish volunteers (ten 4G/4G homozygotes, twenty-eight heterozygotes 4G/5G and twenty-one 5G/5G homozygotes) consumed three diets for periods of 4 weeks each: a SFA-rich diet (38 % fat, 20 % SFA), followed by a carbohydrate-rich diet (30 % fat, 55 % carbohydrate) and a MUFA-rich diet (38 % fat, 22 % MUFA) according to a randomized crossover design. At the end of each dietary period plasma lipid and functional plasma PAI-1 concentrations were determined. Subjects carrying the 4G allele (4G/4G and 4G/5G) showed a significant decrease in PAI-1 concentrations after the MUFA diet, compared with the SFA-rich and carbohydrate-rich diets (genotype x diet interaction: P = 0.028). 5G/5G homozygotes had the lowest plasma PAI-1 concentrations compared with 4G/4G and 4G/5G subjects (genotype: P = 0.002), without any changes as a result of the amount and the quality of the dietary fat. In summary, no differences in plasma PAI-1 concentration response were found after changes in dietary fat intake in 5G/5G homozygotes, although these subjects displayed the lowest concentrations of PAI-1. On the other hand, carriers of the 4G allele are more likely to hyper-respond to the presence of MUFA in the diet because of a greater decrease in PAI-1 concentrations.
Pérez-Martínez
P
P
Lipids and Atherosclerosis Research Unit, Hospital Universitario Reina Sofia, CIBER, Fisiopatologia, Obesidad y Nutricion, Avda. Menendez Pidal, s/n. 14004 Cordoba, Spain. pablopermar@yahoo.es
Adarraga-Cansino
M D
MD
Fernández de la Puebla
R A
RA
Blanco-Molina
A
A
Delgado-Lista
J
J
Marín
C
C
Ordovás
J M
JM
López-Miranda
J
J
Pérez-Jiménez
F
F
D000328:Adult; D000704:Analysis of Variance; D002318:Cardiovascular Diseases / Q000517:prevention & control; D018592:Cross-Over Studies; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage*; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage; D005232:Fatty Acids, Volatile / Q000008:administration & dosage; D005260:Female; D005342:Fibrinolysis; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic; D019518:Postprandial Period
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005229:Fatty Acids, Monounsaturated; D005232:Fatty Acids, Volatile; D008055:Lipids; D017395:Plasminogen Activator Inhibitor 1