ASSOCIATION BETWEEN ALA54THR SUBSTITUTION OF THE FATTY-ACID-BINDING PROTEIN-2 GENE WITH INSULIN-RESISTANCE AND INTRAABDOMINAL FAT THICKNESSIN JAPANESE MEN
K. Yamada et al., ASSOCIATION BETWEEN ALA54THR SUBSTITUTION OF THE FATTY-ACID-BINDING PROTEIN-2 GENE WITH INSULIN-RESISTANCE AND INTRAABDOMINAL FAT THICKNESSIN JAPANESE MEN, Diabetologia, 40(6), 1997, pp. 706-710
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.