The common -675 4G/5G polymorphism in the plasminogen activator inhibitor -1 gene is strongly associated with obesity

Plasminogen activator inhibitor 1 (PAI-1) increases in several insulin-resistant conditions such as obesity. We tested the hypothesis that the PAI-1 gene might be a candidate for obesity and Type II (non-insulin-dependent) diabetes mellitus.

We investigated the frequency of a common and functional -675 4G/5G promoter polymorphism in the PAI-1 gene in 188 lean, 70 overweight (BMI 25-30 kg/m(2)) and 247 obese otherwise healthy Scandinavian subjects.

The genotypic ( p = 0.002), or allelic ( p = 0.0004) distribution differed markedly between the three groups. Homozygosity for 4G was more common among obese people, whereas homozygosity for 5G was more common among lean subjects. Heterozygosity was evenly distributed. The lean and overweight groups did not differ in frequency distribution. The relative risk for being obese in comparison to being lean for 4G/4G was threefold higher ( p = 0.0003). Also, carriers of the 4G allele in the heterozygous or homozygous form were distributed differently between the three groups ( p = 0.006). The 4G carriers were more common among the obese than the lean group. The latter group did not differ from the overweight group. The relative risk of being obese in comparison with lean was twofold increased in 4G carriers ( p = 0.0015). Similar results were obtained in men and women.

Thus, the common -675 4G/5G polymorphism in the PAI-1 gene is strongly linked to obesity and a markedly increased risk for obesity is associated with the 4G allele in its homozygous form.