ASSOCIATION BETWEEN ALA54THR SUBSTITUTION OF THE FATTY-ACID-BINDING PROTEIN-2 GENE WITH INSULIN-RESISTANCE AND INTRAABDOMINAL FAT THICKNESSIN JAPANESE MEN

Alanine to threonine substitution at codon 54 of the fatty acid-bindin g protein 2 (FABP2) gene was recently shown to be associated with insu lin resistance in Pima Indians. It has been hypothesized that the muta tion may result in enhanced intestinal uptake of fatty acids, and ther eby an impairment of insulin action. We analysed the association of th e Ala54Thr substitution with insulin sensitivity and abdominal fat thi ckness in 395 Japanese men aged 50.5 +/- 8.8 years (mean +/- SD) with a body mass index of 24.4 +/- 3.0 kg/m(2). The frequency of the Thr54 allele was 0.34. Although the polymorphism was not significantly assoc iated with diabetes or impaired glucose tolerance, subjects homozygous for the Thr54 allele had higher basal insulin levels. Analysis by hom eostasis model assessment showed an association between the amino acid substitution and greater insulin resistance, and slightly higher beta -cell function. Oral glucose tolerance tests performed in 392 subjects without fasting hyperglycaemia showed higher 2-h insulin concentratio ns in individuals homozygous for the Thr54 allele when compared with h eterozygotes or homozygotes for the Ala54 allele. No significant assoc iation was obtained between the polymorphism of the FABP2 gene and bod y mass index. However, ultrasound measurements of abdominal fat thickn ess revealed a greater accumulation of intra-abdominal fat in subjects homozygous for the Thr54 allele, whereas subcutaneous fat thickness w as not associated with the polymorphism. These observations suggest th at the Ala54Thr substitution in the FABP2 gene is associated with insu lin resistance in Japanese men, and that visceral fat accumulation mig ht be involved in the impaired insulin action associated with the subs titution.