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PAI-1 polymorphisms modulate phenotypes associated with the metabolic syndrome in obese and diabetic Caucasian

C Lopes1, C Dina, E Durand

  • 1Hammersmith Genome Centre, Imperial College, London, UK.

Diabetologia
|July 12, 2003
PubMed

Insights

Genetic variations in plasminogen activator inhibitor-1 (PAI-1) influence metabolic syndrome traits and cardiovascular disease risk. PAI-1 polymorphisms interact with obesity and hyperglycemia to worsen insulin resistance and increase coronary heart disease risk in diabetics.

Area of Science:

  • Genetics
  • Metabolic Syndrome
  • Cardiovascular Disease

Background:

  • Plasminogen activator inhibitor-1 (PAI-1) is a key regulator of fibrinolysis and thrombosis.
  • Understanding the genetic basis of PAI-1 is crucial for its role in metabolic syndrome and related complications.

Purpose of the Study:

  • To investigate the genetic contributions of PAI-1 mutations to metabolic syndrome and its complications.
  • To analyze the association between PAI-1 polymorphisms and metabolic phenotypes.

Main Methods:

  • Screening of PAI-1 promoter and coding sequences for mutations.
  • Genotyping of 1067 French Caucasian individuals with diabetes and obesity.
  • Statistical analysis of PAI-1 polymorphisms and metabolic syndrome phenotypes.

Main Results:

  • Five variants identified: two common promoter polymorphisms (-765 4G/5G, -844 A>G) and three new non-synonymous SNPs (Ala15Thr, Val17Ile, Asn195Ile).
  • Promoter polymorphisms associated with higher fasting glucose and insulin in obese non-diabetics.
  • -844 A>G SNP linked to lower triglycerides and higher HDL cholesterol in lean subjects.
  • PAI-1 polymorphisms showed a trend towards association with coronary heart disease (CHD) in diabetic subjects.

Conclusions:

  • PAI-1 polymorphisms interact with environmental factors like obesity and hyperglycemia.
  • These interactions contribute to a more severe insulin-resistant metabolic profile in overweight individuals.
  • PAI-1 variants may increase CHD risk in diabetic patients.
Abstract

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